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9. Transgenic inhibition of astroglial NF-κB protects from optic nerve damage and retinal ganglion cell loss in experimental optic neuritis

Author

Brambilla Roberta, Dvoriantchikova Galina, Barakat David, Ivanov Dmitry, Bethea John R, and Shestopalov Valery I

Subjects
Optic neuritis, Astrogliosis, Retinal ganglion cell death, NF-κB pathway, Neurology. Diseases of the nervous system, RC346-429
Abstract

Abstract Background Optic neuritis is an acute, demyelinating neuropathy of the optic nerve often representing the first appreciable symptom of multiple sclerosis. Wallerian degeneration of irreversibly damaged optic nerve axons leads to death of retinal ganglion cells, which is the cause of permanent visual impairment. Although the specific mechanisms responsible for triggering these events are unknown, it has been suggested that a key pathological factor is the activation of immune-inflammatory processes secondary to leukocyte infiltration. However, to date, there is no conclusive evidence to support such a causal role for infiltrating peripheral immune cells in the etiopathology of optic neuritis. Methods To dissect the contribution of the peripheral immune-inflammatory response versus the CNS-specific inflammatory response in the development of optic neuritis, we analyzed optic nerve and retinal ganglion cells pathology in wild-type and GFAP-IκBα-dn transgenic mice, where NF-κB is selectively inactivated in astrocytes, following induction of EAE. Results We found that, in wild-type mice, axonal demyelination in the optic nerve occurred as early as 8 days post induction of EAE, prior to the earliest signs of leukocyte infiltration (20 days post induction). On the contrary, GFAP-IκBα-dn mice were significantly protected and showed a nearly complete prevention of axonal demyelination, as well as a drastic attenuation in retinal ganglion cell death. This correlated with a decrease in the expression of pro-inflammatory cytokines, chemokines, adhesion molecules, as well as a prevention of NAD(P)H oxidase subunit upregulation. Conclusions Our results provide evidence that astrocytes, not infiltrating immune cells, play a key role in the development of optic neuritis and that astrocyte-mediated neurotoxicity is dependent on activation of a transcriptional program regulated by NF-κB. Hence, interventions targeting the NF-κB transcription factor in astroglia may be of therapeutic value in the treatment of optic neuritis associated with multiple sclerosis.

Published
2012
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11. 31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016): part two

Author

Ager, Casey, Reilley, Matthew, Nicholas, Courtney, Bartkowiak, Todd, Jaiswal, Ashvin, Curran, Michael, Albershardt, Tina C., Bajaj, Anshika, Archer, Jacob F., Reeves, Rebecca S., Ngo, Lisa Y., Berglund, Peter, ter Meulen, Jan, Denis, Caroline, Ghadially, Hormas, Arnoux, Thomas, Chanuc, Fabien, Fuseri, Nicolas, Wilkinson, Robert W., Wagtmann, Nicolai, Morel, Yannis, Andre, Pascale, Atkins, Michael B., Carlino, Matteo S., Ribas, Antoni, Thompson, John A., Choueiri, Toni K., Hodi, F. Stephen, Hwu, Wen-Jen, McDermott, David F., Atkinson, Victoria, Cebon, Jonathan S., Fitzharris, Bernie, Jameson, Michael B., McNeil, Catriona, Hill, Andrew G., Mangin, Eric, Ahamadi, Malidi, van Vugt, Marianne, van Zutphen, Mariëlle, Ibrahim, Nageatte, Long, Georgina V., Gartrell, Robyn, Blake, Zoe, Simoes, Ines, Fu, Yichun, Saito, Takuro, Qian, Yingzhi, Lu, Yan, Saenger, Yvonne M., Budhu, Sadna, De Henau, Olivier, Zappasodi, Roberta, Schlunegger, Kyle, Freimark, Bruce, Hutchins, Jeff, Barker, Christopher A., Wolchok, Jedd D., Merghoub, Taha, Burova, Elena, Allbritton, Omaira, Hong, Peter, Dai, Jie, Pei, Jerry, Liu, Matt, Kantrowitz, Joel, Lai, Venus, Poueymirou, William, MacDonald, Douglas, Ioffe, Ella, Mohrs, Markus, Olson, William, Thurston, Gavin, Capasso, Cristian, Frascaro, Federica, Carpi, Sara, Tähtinen, Siri, Feola, Sara, Fusciello, Manlio, Peltonen, Karita, Martins, Beatriz, Sjöberg, Madeleine, Pesonen, Sari, Ranki, Tuuli, Kyruk, Lukasz, Ylösmäki, Erkko, Cerullo, Vincenzo, Cerignoli, Fabio, Xi, Biao, Guenther, Garret, Yu, Naichen, Muir, Lincoln, Zhao, Leyna, Abassi, Yama, Cervera-Carrascón, Víctor, Siurala, Mikko, Santos, João, Havunen, Riikka, Parviainen, Suvi, Hemminki, Akseli, Dalgleish, Angus, Mudan, Satvinder, DeBenedette, Mark, Plachco, Ana, Gamble, Alicia, Grogan, Elizabeth W., Krisko, John, Tcherepanova, Irina, Nicolette, Charles, Dhupkar, Pooja, Yu, Ling, Kleinerman, Eugenie S., Gordon, Nancy, Grenga, Italia, Lepone, Lauren, Gameiro, Sofia, Knudson, Karin M., Fantini, Massimo, Tsang, Kwong, Hodge, James, Donahue, Renee, Schlom, Jeffrey, Evans, Elizabeth, Bussler, Holm, Mallow, Crystal, Reilly, Christine, Torno, Sebold, Scrivens, Maria, Foster, Cathie, Howell, Alan, Balch, Leslie, Knapp, Alyssa, Leonard, John E., Paris, Mark, Fisher, Terry, Hu-Lieskovan, Siwen, Smith, Ernest, Zauderer, Maurice, Fogler, William, Franklin, Marilyn, Thayer, Matt, Saims, Dan, Magnani, John L., Gong, Jian, Gray, Michael, Fromm, George, de Silva, Suresh, Giffin, Louise, Xu, Xin, Rose, Jason, Schreiber, Taylor H., Gameiro, Sofia R., Clavijo, Paul E., Allen, Clint T., Hodge, James W., Tsang, Kwong Y., Grogan, Jane, Manieri, Nicholas, Chiang, Eugene, Caplazi, Patrick, Yadav, Mahesh, Hagner, Patrick, Chiu, Hsiling, Waldman, Michelle, Klippel, Anke, Thakurta, Anjan, Pourdehnad, Michael, Gandhi, Anita, Henrich, Ian, Quick, Laura, Young, Rob, Chou, Margaret, Hotson, Andrew, Willingham, Stephen, Ho, Po, Choy, Carmen, Laport, Ginna, McCaffery, Ian, Miller, Richard, Tipton, Kimberly A., Wong, Kenneth R., Singson, Victoria, Wong, Chihunt, Chan, Chanty, Huang, Yuanhiu, Liu, Shouchun, Richardson, Jennifer H., Kavanaugh, W. Michael, West, James, Irving, Bryan A., Jaini, Ritika, Loya, Matthew, Eng, Charis, Johnson, Melissa L., Adjei, Alex A., Opyrchal, Mateusz, Ramalingam, Suresh, Janne, Pasi A., Dominguez, George, Gabrilovich, Dmitry, de Leon, Laura, Hasapidis, Jeannette, Diede, Scott J., Ordentlich, Peter, Cruickshank, Scott, Meyers, Michael L., Hellmann, Matthew D., Kalinski, Pawel, Zureikat, Amer, Edwards, Robert, Muthuswamy, Ravi, Obermajer, Nataša, Urban, Julie, Butterfield, Lisa H., Gooding, William, Zeh, Herbert, Bartlett, David, Zubkova, Olga, Agapova, Larissa, Kapralova, Marina, Krasovskaia, Liudmila, Ovsepyan, Armen, Lykov, Maxim, Eremeev, Artem, Bokovanov, Vladimir, Grigoryeva, Olga, Karpov, Andrey, Ruchko, Sergey, Shuster, Alexandr, Khalil, Danny N., Campesato, Luis Felipe, Li, Yanyun, Lazorchak, Adam S., Patterson, Troy D., Ding, Yueyun, Sasikumar, Pottayil, Sudarshan, Naremaddepalli, Gowda, Nagaraj, Ramachandra, Raghuveer, Samiulla, Dodheri, Giri, Sanjeev, Eswarappa, Rajesh, Ramachandra, Murali, Tuck, David, Wyant, Timothy, Leshem, Jasmin, Liu, Xiu-fen, Bera, Tapan, Terabe, Masaki, Bossenmaier, Birgit, Niederfellner, Gerhard, Reiter, Yoram, Pastan, Ira, Xia, Leiming, Xia, Yang, Hu, Yangyang, Wang, Yi, Bao, Yangyi, Dai, Fu, Huang, Shiang, Hurt, Elaine, Hollingsworth, Robert E., Lum, Lawrence G., Chang, Alfred E., Wicha, Max S., Li, Qiao, Mace, Thomas, Makhijani, Neil, Talbert, Erin, Young, Gregory, Guttridge, Denis, Conwell, Darwin, Lesinski, Gregory B., Gonzales, Rodney JM Macedo, Huffman, Austin P., Wang, Ximi K., Reshef, Ran, MacKinnon, Andy, Chen, Jason, Gross, Matt, Marguier, Gisele, Shwonek, Peter, Sotirovska, Natalija, Steggerda, Susanne, Parlati, Francesco, Makkouk, Amani, Bennett, Mark K., Emberley, Ethan, Huang, Tony, Li, Weiqun, Neou, Silinda, Pan, Alison, Zhang, Jing, Zhang, Winter, Marshall, Netonia, Marron, Thomas U., Agudo, Judith, Brown, Brian, Brody, Joshua, McQuinn, Christopher, Farren, Matthew, Komar, Hannah, Shakya, Reena, Ludwug, Thomas, Morillon, Y. Maurice, Hammond, Scott A., Greiner, John W., Nath, Pulak R., Schwartz, Anthony L., Maric, Dragan, Roberts, David D., Naing, Aung, Papadopoulos, Kyriakos P., Autio, Karen A., Wong, Deborah J., Patel, Manish, Falchook, Gerald, Pant, Shubham, Ott, Patrick A., Whiteside, Melinda, Patnaik, Amita, Mumm, John, Janku, Filip, Chan, Ivan, Bauer, Todd, Colen, Rivka, VanVlasselaer, Peter, Brown, Gail L., Tannir, Nizar M., Oft, Martin, Infante, Jeffrey, Lipson, Evan, Gopal, Ajay, Neelapu, Sattva S., Armand, Philippe, Spurgeon, Stephen, Leonard, John P., Sanborn, Rachel E., Melero, Ignacio, Gajewski, Thomas F., Maurer, Matthew, Perna, Serena, Gutierrez, Andres A., Clynes, Raphael, Mitra, Priyam, Suryawanshi, Satyendra, Gladstone, Douglas, Callahan, Margaret K., Crooks, James, Brown, Sheila, Gauthier, Audrey, de Boisferon, Marc Hillairet, MacDonald, Andrew, Brunet, Laura Rosa, Rothwell, William T., Bell, Peter, Wilson, James M., Sato-Kaneko, Fumi, Yao, Shiyin, Zhang, Shannon S., Carson, Dennis A., Guiducci, Cristina, Coffman, Robert L., Kitaura, Kazutaka, Matsutani, Takaji, Suzuki, Ryuji, Hayashi, Tomoko, Cohen, Ezra E. W., Schaer, David, Li, Yanxia, Dobkin, Julie, Amatulli, Michael, Hall, Gerald, Doman, Thompson, Manro, Jason, Dorsey, Frank Charles, Sams, Lillian, Holmgaard, Rikke, Persaud, Krishnadatt, Ludwig, Dale, Surguladze, David, Kauh, John S., Novosiadly, Ruslan, Kalos, Michael, Driscoll, Kyla, Pandha, Hardev, Ralph, Christy, Harrington, Kevin, Curti, Brendan, Akerley, Wallace, Gupta, Sumati, Melcher, Alan, Mansfield, David, Kaufman, David R., Schmidt, Emmett, Grose, Mark, Davies, Bronwyn, Karpathy, Roberta, Shafren, Darren, Shamalov, Katerina, Cohen, Cyrille, Sharma, Naveen, Allison, James, Shekarian, Tala, Valsesia-Wittmann, Sandrine, Caux, Christophe, Marabelle, Aurelien, Slomovitz, Brian M., Moore, Kathleen M., Youssoufian, Hagop, Posner, Marshall, Tewary, Poonam, Brooks, Alan D., Xu, Ya-Ming, Wijeratne, Kithsiri, Gunatilaka, Leslie A. A., Sayers, Thomas J., Vasilakos, John P., Alston, Tesha, Dovedi, Simon, Elvecrog, James, Grigsby, Iwen, Herbst, Ronald, Johnson, Karen, Moeckly, Craig, Mullins, Stefanie, Siebenaler, Kristen, SternJohn, Julius, Tilahun, Ashenafi, Tomai, Mark A., Vogel, Katharina, Vietsch, Eveline E., Wellstein, Anton, Wythes, Martin, Crosignani, Stefano, Tumang, Joseph, Alekar, Shilpa, Bingham, Patrick, Cauwenberghs, Sandra, Chaplin, Jenny, Dalvie, Deepak, Denies, Sofie, De Maeseneire, Coraline, Feng, JunLi, Frederix, Kim, Greasley, Samantha, Guo, Jie, Hardwick, James, Kaiser, Stephen, Jessen, Katti, Kindt, Erick, Letellier, Marie-Claire, Li, Wenlin, Maegley, Karen, Marillier, Reece, Miller, Nichol, Murray, Brion, Pirson, Romain, Preillon, Julie, Rabolli, Virginie, Ray, Chad, Ryan, Kevin, Scales, Stephanie, Srirangam, Jay, Solowiej, Jim, Stewart, Al, Streiner, Nicole, Torti, Vince, Tsaparikos, Konstantinos, Zheng, Xianxian, Driessens, Gregory, Gomes, Bruno, Kraus, Manfred, Xu, Chunxiao, Zhang, Yanping, Kradjian, Giorgio, Qin, Guozhong, Qi, Jin, Xu, Xiaomei, Marelli, Bo, Yu, Huakui, Guzman, Wilson, Tighe, Rober, Salazar, Rachel, Lo, Kin-Ming, English, Jessie, Radvanyi, Laszlo, Lan, Yan, Postow, Michael, Senbabaoglu, Yasin, Gasmi, Billel, Zhong, Hong, Liu, Cailian, Hirschhorhn-Cymerman, Daniel, Zha, Yuanyuan, Malnassy, Gregory, Fulton, Noreen, Park, Jae-Hyun, Stock, Wendy, Nakamura, Yusuke, Liu, Hongtao, Ju, Xiaoming, Kosoff, Rachelle, Ramos, Kimberly, Coder, Brandon, Petit, Robert, Princiotta, Michael, Perry, Kyle, Zou, Jun, Arina, Ainhoa, Fernandez, Christian, Zheng, Wenxin, Beckett, Michael A., Mauceri, Helena J., Fu, Yang-Xin, Weichselbaum, Ralph R., Lewis, Whitney, Han, Yanyan, Wu, Yeting, Yang, Chou, Huang, Jing, Wu, Dongyun, Li, Jin, Liang, Xiaoling, Zhou, Xiangjun, Hou, Jinlin, Hassan, Raffit, Jahan, Thierry, Antonia, Scott J., Kindler, Hedy L., Alley, Evan W., Honarmand, Somayeh, Liu, Weiqun, Leong, Meredith L., Whiting, Chan C., Nair, Nitya, Enstrom, Amanda, Lemmens, Edward E., Tsujikawa, Takahiro, Kumar, Sushil, Coussens, Lisa M., Murphy, Aimee L., Brockstedt, Dirk G., Koch, Sven D., Sebastian, Martin, Weiss, Christian, Früh, Martin, Pless, Miklos, Cathomas, Richard, Hilbe, Wolfgang, Pall, Georg, Wehler, Thomas, Alt, Jürgen, Bischoff, Helge, Geissler, Michael, Griesinger, Frank, Kollmeier, Jens, Papachristofilou, Alexandros, Doener, Fatma, Fotin-Mleczek, Mariola, Hipp, Madeleine, Hong, Henoch S., Kallen, Karl-Josef, Klinkhardt, Ute, Stosnach, Claudia, Scheel, Birgit, Schroeder, Andreas, Seibel, Tobias, Gnad-Vogt, Ulrike, Zippelius, Alfred, Park, Ha-Ram, Ahn, Yong-Oon, Kim, Tae Min, Kim, Soyeon, Kim, Seulki, Lee, Yu Soo, Keam, Bhumsuk, Kim, Dong-Wan, Heo, Dae Seog, Pilon-Thomas, Shari, Weber, Amy, Morse, Jennifer, Kodumudi, Krithika, Liu, Hao, Mullinax, John, Sarnaik, Amod A., Pike, Luke, Bang, Andrew, Balboni, Tracy, Taylor, Allison, Spektor, Alexander, Wilhite, Tyler, Krishnan, Monica, Cagney, Daniel, Alexander, Brian, Aizer, Ayal, Buchbinder, Elizabeth, Awad, Mark, Ghandi, Leena, Schoenfeld, Jonathan, Lessey-Morillon, Elizabeth, Ridnour, Lisa, Segal, Neil H., Sharma, Manish, Le, Dung T., Ferris, Robert L., Zelenetz, Andrew D., Levy, Ronald, Lossos, Izidore S., Jacobson, Caron, Ramchandren, Radhakrishnan, Godwin, John, Colevas, A. Dimitrios, Meier, Roland, Krishnan, Suba, Gu, Xuemin, Neely, Jaclyn, Timmerman, John, Vanpouille-Box, Claire I., Formenti, Silvia C., Demaria, Sandra, Wennerberg, Erik, Mediero, Aranzazu, Cronstein, Bruce N., Gustafson, Michael P., DiCostanzo, AriCeli, Wheatley, Courtney, Kim, Chul-Ho, Bornschlegl, Svetlana, Gastineau, Dennis A., Johnson, Bruce D., Dietz, Allan B., MacDonald, Cameron, Bucsek, Mark, Qiao, Guanxi, Hylander, Bonnie, Repasky, Elizabeth, Turbitt, William J., Xu, Yitong, Mastro, Andrea, Rogers, Connie J., Withers, Sita, Wang, Ziming, Khuat, Lam T., Dunai, Cordelia, Blazar, Bruce R., Longo, Dan, Rebhun, Robert, Grossenbacher, Steven K., Monjazeb, Arta, Murphy, William J., Rowlinson, Scott, Agnello, Giulia, Alters, Susan, Lowe, David, Scharping, Nicole, Menk, Ashley V., Whetstone, Ryan, Zeng, Xue, Delgoffe, Greg M., Santos, Patricia M., Shi, Jian, Delgoffe, Greg, Nagasaka, Misako, Sukari, Ammar, Byrne-Steele, Miranda, Pan, Wenjing, Hou, Xiaohong, Brown, Brittany, Eisenhower, Mary, Han, Jian, Collins, Natalie, Manguso, Robert, Pope, Hans, Shrestha, Yashaswi, Boehm, Jesse, Haining, W. Nicholas, Cron, Kyle R., Sivan, Ayelet, Aquino-Michaels, Keston, Orecchioni, Marco, Bedognetti, Davide, Hendrickx, Wouter, Fuoco, Claudia, Spada, Filomena, Sgarrella, Francesco, Cesareni, Gianni, Marincola, Francesco, Kostarelos, Kostas, Bianco, Alberto, Delogu, Lucia, Roelands, Jessica, Boughorbel, Sabri, Decock, Julie, Presnell, Scott, Wang, Ena, Marincola, Franco M., Kuppen, Peter, Ceccarelli, Michele, Rinchai, Darawan, Chaussabel, Damien, Miller, Lance, Nguyen, Andrew, Sanborn, J. Zachary, Vaske, Charles, Rabizadeh, Shahrooz, Niazi, Kayvan, Benz, Steven, Patel, Shashank, Restifo, Nicholas, White, James, Angiuoli, Sam, Sausen, Mark, Jones, Sian, Sevdali, Maria, Simmons, John, Velculescu, Victor, Diaz, Luis, Zhang, Theresa, Sims, Jennifer S., Barton, Sunjay M., Kadenhe-Chiweshe, Angela, Dela Cruz, Filemon, Turk, Andrew T., Mazzeo, Christopher F., Kung, Andrew L., Bruce, Jeffrey N., Yamashiro, Darrell J., Connolly, Eileen P., Baird, Jason, Crittenden, Marka, Friedman, David, Xiao, Hong, Leidner, Rom, Bell, Bryan, Young, Kristina, Gough, Michael, Bian, Zhen, Kidder, Koby, Liu, Yuan, Curran, Emily, Chen, Xiufen, Corrales, Leticia P., Kline, Justin, Aguilar, Ethan G., Guerriero, Jennifer, Sotayo, Alaba, Ponichtera, Holly, Pourzia, Alexandra, Schad, Sara, Carrasco, Ruben, Lazo, Suzan, Bronson, Roderick, Letai, Anthony, Kornbluth, Richard S., Gupta, Sachin, Termini, James, Guirado, Elizabeth, Stone, Geoffrey W., Meyer, Christina, Helming, Laura, Wilson, Nicholas, Hofmeister, Robert, Neubert, Natalie J., Tillé, Laure, Barras, David, Soneson, Charlotte, Baumgaertner, Petra, Rimoldi, Donata, Gfeller, David, Delorenzi, Mauro, Fuertes Marraco, Silvia A., Speiser, Daniel E., Abraham, Tara S., Xiang, Bo, Magee, Michael S., Waldman, Scott A., Snook, Adam E., Blogowski, Wojciech, Zuba-Surma, Ewa, Budkowska, Marta, Salata, Daria, Dolegowska, Barbara, Starzynska, Teresa, Chan, Leo, Somanchi, Srinivas, McCulley, Kelsey, Lee, Dean, Buettner, Nico, Shi, Feng, Myers, Paisley T., Curbishley, Stuart, Penny, Sarah A., Steadman, Lora, Millar, David, Speers, Ellen, Ruth, Nicola, Wong, Gabriel, Thimme, Robert, Adams, David, Cobbold, Mark, Thomas, Remy, Al-Muftah, Mariam, Wong, Michael KK, Morse, Michael, Clark, Joseph I., Kaufman, Howard L., Daniels, Gregory A., Hua, Hong, Rao, Tharak, Dutcher, Janice P., Kang, Kai, Saunthararajah, Yogen, Velcheti, Vamsidhar, Kumar, Vikas, Anwar, Firoz, Verma, Amita, Chheda, Zinal, Kohanbash, Gary, Sidney, John, Okada, Kaori, Shrivastav, Shruti, Carrera, Diego A., Liu, Shuming, Jahan, Naznin, Mueller, Sabine, Pollack, Ian F., Carcaboso, Angel M., Sette, Alessandro, Hou, Yafei, Okada, Hideho, Field, Jessica J., Zeng, Weiping, Shih, Vincent FS, Law, Che-Leung, Senter, Peter D., Gardai, Shyra J., Okeley, Nicole M., Abelin, Jennifer G., Saeed, Abu Z., Malaker, Stacy A., Shabanowitz, Jeffrey, Ward, Stephen T., Hunt, Donald F., Profusek, Pam, Wood, Laura, Shepard, Dale, Grivas, Petros, Kapp, Kerstin, Volz, Barbara, Oswald, Detlef, Wittig, Burghardt, Schmidt, Manuel, Sefrin, Julian P., Hillringhaus, Lars, Lifke, Valeria, Lifke, Alexander, Skaletskaya, Anna, Ponte, Jose, Chittenden, Thomas, Setiady, Yulius, Sivado, Eva, Thomas, Vincent, El Alaoui, Meddy, Papot, Sébastien, Dumontet, Charles, Dyson, Mike, McCafferty, John, El Alaoui, Said, Bommareddy, Praveen K., Zloza, Andrew, Kohlhapp, Frederick, Silk, Ann W., Jhawar, Sachin, Paneque, Tomas, Newman, Jenna, Beltran, Pedro, Cao, Felicia, Hong, Bang-Xing, Rodriguez-Cruz, Tania, Song, Xiao-Tong, Gottschalk, Stephen, Calderon, Hugo, Illingworth, Sam, Brown, Alice, Fisher, Kerry, Seymour, Len, Champion, Brian, Eriksson, Emma, Wenthe, Jessica, Hellström, Ann-Charlotte, Paul-Wetterberg, Gabriella, Loskog, Angelica, Milenova, Ioanna, Ståhle, Magnus, Jarblad-Leja, Justyna, Ullenhag, Gustav, Dimberg, Anna, Moreno, Rafael, Alemany, Ramon, Goyal, Sharad, Silk, Ann, Mehnert, Janice, Gabrail, Nashat, Bryan, Jennifer, Medina, Daniel, Mitchell, Leah, Yagiz, Kader, Lopez, Fernando, Mendoza, Daniel, Munday, Anthony, Gruber, Harry, Jolly, Douglas, Fuhrmann, Steven, Radoja, Sasa, Tan, Wei, Pourchet, Aldo, Frey, Alan, Mohr, Ian, Mulvey, Matthew, Andtbacka, Robert H. I., Ross, Merrick, Agarwala, Sanjiv, Grossmann, Kenneth, Taylor, Matthew, Vetto, John, Neves, Rogerio, Daud, Adil, Khong, Hung, Meek, Stephanie M., Ungerleider, Richard, Welden, Scott, Tanaka, Maki, Williams, Matthew, Hallmeyer, Sigrun, Fox, Bernard, Feng, Zipei, Paustian, Christopher, Bifulco, Carlo, Zafar, Sadia, Hemminki, Otto, Bramante, Simona, Vassilev, Lotta, Wang, Hongjie, Lieber, Andre, Hemmi, Silvio, de Gruijl, Tanja, Kanerva, Anna, Ansari, Tameem, Sundararaman, Srividya, Roen, Diana, Lehmann, Paul, Bloom, Anja C., Bender, Lewis H., Walters, Ian B., Berzofsky, Jay A., Chapelin, Fanny, Ahrens, Eric T., DeFalco, Jeff, Harbell, Michael, Manning-Bog, Amy, Scholz, Alexander, Zhang, Danhui, Baia, Gilson, Tan, Yann Chong, Sokolove, Jeremy, Kim, Dongkyoon, Williamson, Kevin, Chen, Xiaomu, Colrain, Jillian, Santo, Gregg Espiritu, Nguyen, Ngan, Volkmuth, Wayne, Greenberg, Norman, Robinson, William, Emerling, Daniel, Drake, Charles G., Petrylak, Daniel P., Antonarakis, Emmanuel S., Kibel, Adam S., Chang, Nancy N., Vu, Tuyen, Campogan, Dwayne, Haynes, Heather, Trager, James B., Sheikh, Nadeem A., Quinn, David I., Kirk, Peter, Addepalli, Murali, Chang, Thomas, Zhang, Ping, Konakova, Marina, Hagihara, Katsunobu, Pai, Steven, VanderVeen, Laurie, Obalapur, Palakshi, Kuo, Peiwen, Quach, Phi, Fong, Lawrence, Charych, Deborah H., Zalevsky, Jonathan, Langowski, John L., Kirksey, Yolanda, Nutakki, Ravi, Kolarkar, Shalini, Pena, Rhoneil, Hoch, Ute, Doberstein, Stephen K., Cha, John, Mallon, Zach, Perez, Myra, McDaniel, Amanda, Anand, Snjezana, Uecker, Darrin, Nuccitelli, Richard, Wieckowski, Eva, Muthuswamy, Ravikumar, Ravindranathan, Roshni, Renrick, Ariana N., Thounaojam, Menaka, Thomas, Portia, Pellom, Samuel, Shanker, Anil, Dudimah, Duafalia, Brooks, Alan, Su, Yu-Lin, Adamus, Tomasz, Zhang, Qifang, Nechaev, Sergey, Kortylewski, Marcin, Wei, Spencer, Anderson, Clark, Tang, Chad, Schoenhals, Jonathan, Tsouko, Efrosini, Heymach, John, de Groot, Patricia, Chang, Joe, Hess, Kenneth R., Diab, Adi, Sharma, Padmanee, Hong, David, Welsh, James, Parsons, Andrea J., Leleux, Jardin, Ascarateil, Stephane, Koziol, Marie Eve, Bai, Dina, Dai, Peihong, Wang, Weiyi, Yang, Ning, Shuman, Stewart, Deng, Liang, Dillon, Patrick, Petroni, Gina, Brenin, David, Bullock, Kim, Olson, Walter, Smolkin, Mark E., Smith, Kelly, Nail, Carmel, Slingluff, Craig L., Sharma, Meenu, Fa’ak, Faisal, Janssen, Louise, Khong, Hiep, Xiao, Zhilan, Hailemichael, Yared, Singh, Manisha, Vianden, Christina, Overwijk, Willem W., Facciabene, Andrea, Stefano, Pierini, Chongyung, Fang, Rafail, Stavros, Nielsen, Michael, Vanderslice, Peter, Woodside, Darren G., Market, Robert V., Biediger, Ronald J., Marathi, Upendra K., Hollevoet, Kevin, Geukens, Nick, Declerck, Paul, Joly, Nathalie, McIntosh, Laura, Paramithiotis, Eustache, Rizell, Magnus, Sternby, Malin, Andersson, Bengt, Karlsson-Parra, Alex, Kuai, Rui, Ochyl, Lukasz, Schwendeman, Anna, Moon, James, Deng, Weiwen, Hudson, Thomas E., Hanson, Bill, Rae, Chris S., Burrill, Joel, Skoble, Justin, Katibah, George, deVries, Michele, Lauer, Peter, Dubensky, Thomas W., Chen, Xin, Zhou, Li, Ren, Xiubao, Aggarwal, Charu, Mangrolia, Drishty, Cohen, Roger, Weinstein, Gregory, Morrow, Matthew, Bauml, Joshua, Kraynyak, Kim, Boyer, Jean, Yan, Jian, Lee, Jessica, Humeau, Laurent, Oyola, Sandra, Duff, Susan, Weiner, David, Yang, Zane, Bagarazzi, Mark, McNeel, Douglas G., Eickhoff, Jens, Jeraj, Robert, Staab, Mary Jane, Straus, Jane, Rekoske, Brian, Liu, Glenn, Melssen, Marit, Grosh, William, Varhegyi, Nikole, Galeassi, Nadejda, Deacon, Donna H., Gaughan, Elizabeth, Ghisoli, Maurizio, Barve, Minal, Mennel, Robert, Wallraven, Gladice, Manning, Luisa, Senzer, Neil, Nemunaitis, John, Ogasawara, Masahiro, Ota, Shuichi, Peace, Kaitlin M., Hale, Diane F., Vreeland, Timothy J., Jackson, Doreen O., Berry, John S., Trappey, Alfred F., Herbert, Garth S., Clifton, Guy T., Hardin, Mark O., Toms, Anne, Qiao, Na, Litton, Jennifer, Peoples, George E., Mittendorf, Elizabeth A., Ghamsari, Lila, Flano, Emilio, Jacques, Judy, Liu, Biao, Havel, Jonathan, Makarov, Vladimir, Chan, Timothy A., Flechtner, Jessica B., Facciponte, John, Ugel, Stefano, De Sanctis, Francesco, Coukos, George, Paris, Sébastien, Pottier, Agnes, Levy, Laurent, Lu, Bo, Cappuccini, Federica, Pollock, Emily, Bryant, Richard, Hamdy, Freddie, Hill, Adrian, Redchenko, Irina, Sultan, Hussein, Kumai, Takumi, Fesenkova, Valentyna, Celis, Esteban, Fernando, Ingrid, Palena, Claudia, David, Justin M., Gabitzsch, Elizabeth, Jones, Frank, Gulley, James L., Herranz, Mireia Uribe, Wada, Hiroshi, Shimizu, Atsushi, Osada, Toshihiro, Fukaya, Satoshi, Sasaki, Eiji, Abolhalaj, Milad, Askmyr, David, Lundberg, Kristina, Albrekt, Ann-Sofie, Greiff, Lennart, Lindstedt, Malin, Flies, Dallas B., Higuchi, Tomoe, Ornatowski, Wojciech, Harris, Jaryse, Adams, Sarah F., Aguilera, Todd, Rafat, Marjan, Castellini, Laura, Shehade, Hussein, Kariolis, Mihalis, Jang, Dadi, vonEbyen, Rie, Graves, Edward, Ellies, Lesley, Rankin, Erinn, Koong, Albert, Giaccia, Amato, Ajina, Reham, Wang, Shangzi, Smith, Jill, Pierobon, Mariaelena, Jablonski, Sandra, Petricoin, Emanuel, Weiner, Louis M., Sherry, Lorcan, Waller, John, Anderson, Mark, Bigley, Alison, Bernatchez, Chantale, Haymaker, Cara, Kluger, Harriet, Tetzlaff, Michael, Jackson, Natalie, Gergel, Ivan, Tagliaferri, Mary, Hwu, Patrick, Snzol, Mario, Hurwitz, Michael, Barberi, Theresa, Martin, Allison, Suresh, Rahul, Barakat, David, Harris-Bookman, Sarah, Drake, Charles, Friedman, Alan, Berkey, Sara, Downs-Canner, Stephanie, Edwards, Robert P., Curiel, Tyler, Odunsi, Kunle, Bruno, Tullia C., Moore, Brandon, Squalls, Olivia, Ebner, Peggy, Waugh, Katherine, Mitchell, John, Franklin, Wilbur, Merrick, Daniel, McCarter, Martin, Palmer, Brent, Kern, Jeffrey, Vignali, Dario, Slansky, Jill, Chan, Anissa S. H., Qiu, Xiaohong, Fraser, Kathryn, Jonas, Adria, Ottoson, Nadine, Gordon, Keith, Kangas, Takashi O., Leonardo, Steven, Ertelt, Kathleen, Walsh, Richard, Uhlik, Mark, Graff, Jeremy, Bose, Nandita, Gupta, Ravi, Mandloi, Nitin, Paul, Kiran, Patil, Ashwini, Sathian, Rekha, Mohan, Aparna, Manoharan, Malini, Chaudhuri, Amitabha, Chen, Yu, Lin, Jing, Ye, Yun-bin, Xu, Chun-wei, Chen, Gang, Guo, Zeng-qing, Komarov, Andrey, Chenchik, Alex, Makhanov, Michael, Frangou, Costa, Zheng, Yi, Coltharp, Carla, Unfricht, Darryn, Dilworth, Ryan, Fridman, Leticia, Liu, Linying, Rajopadhye, Milind, Miller, Peter, Concha-Benavente, Fernando, Bauman, Julie, Trivedi, Sumita, Srivastava, Raghvendra, Ohr, James, Heron, Dwight, Duvvuri, Uma, Kim, Seungwon, Torrey, Heather, Mera, Toshi, Okubo, Yoshiaki, Vanamee, Eva, Foster, Rosemary, Faustman, Denise, Stack, Edward, Izaki, Daisuke, Beck, Kristen, Jia, Dan Tong, Armenta, Paul, White-Stern, Ashley, Marks, Douglas, Taback, Bret, Horst, Basil, Glickman, Laura Hix, Kanne, David B., Gauthier, Kelsey S., Desbien, Anthony L., Francica, Brian, Leong, Justin L., Sung, Leonard, Metchette, Ken, Kasibhatla, Shailaja, Pferdekamper, Anne Marie, Zheng, Lianxing, Cho, Charles, Feng, Yan, McKenna, Jeffery M., Tallarico, John, Bender, Steven, Ndubaku, Chudi, McWhirter, Sarah M., Gugel, Elena Gonzalez, Bell, Charles J. M., Munk, Adiel, Muniz, Luciana, Bhardwaj, Nina, Zhao, Fei, Evans, Kathy, Xiao, Christine, Holtzhausen, Alisha, Hanks, Brent A., Scholler, Nathalie, Yin, Catherine, Van der Meijs, Pien, Prantner, Andrew M., Krejsa, Cecile M., Smith, Leia, Johnson, Brian, Branstetter, Daniel, Stein, Paul L., Jaen, Juan C., Tan, Joanne BL, Chen, Ada, Park, Timothy, Powers, Jay P., Sexton, Holly, Xu, Guifen, Young, Steve W., Schindler, Ulrike, Deng, Wentao, Klinke, David John, Komar, Hannah M., Serpa, Gregory, Elnaggar, Omar, Hart, Philip, Schmidt, Carl, Dillhoff, Mary, Jin, Ming, Ostrowski, Michael C., Koti, Madhuri, Au, Katrina, Peterson, Nichole, Truesdell, Peter, Reid-Schachter, Gillian, Graham, Charles, Craig, Andrew, Francis, Julie-Ann, Kotlan, Beatrix, Balatoni, Timea, Farkas, Emil, Toth, Laszlo, Ujhelyi, Mihaly, Savolt, Akos, Doleschall, Zoltan, Horvath, Szabolcs, Eles, Klara, Olasz, Judit, Csuka, Orsolya, Kasler, Miklos, Liszkay, Gabriella, Barnea, Eytan, Blakely, Collin, Flynn, Patrick, Goodman, Reid, Bueno, Raphael, Sugarbaker, David, Jablons, David, Broaddus, V. Courtney, West, Brian, Kunk, Paul R., Obeid, Joseph M., Winters, Kevin, Pramoonjago, Patcharin, Stelow, Edward B., Bauer, Todd W., Rahma, Osama E., Lamble, Adam, Kosaka, Yoko, Huang, Fei, Saser, Kate A., Adams, Homer, Tognon, Christina E., Laderas, Ted, McWeeney, Shannon, Loriaux, Marc, Tyner, Jeffery W., Druker, Brian J., Lind, Evan F., Liu, Zhuqing, Lu, Shanhong, Kane, Lawrence P., Shayan, Gulidanna, Femel, Julia, Lane, Ryan, Booth, Jamie, Lund, Amanda W., Rodriguez, Anthony, Engelhard, Victor H., Metelli, Alessandra, Wu, Bill X., Fugle, Caroline W., Saleh, Rachidi, Sun, Shaoli, Wu, Jennifer, Liu, Bei, Li, Zihai, Morris, Zachary S., Guy, Emily I., Heinze, Clinton, Kler, Jasdeep, Gressett, Monica M., Werner, Lauryn R., Gillies, Stephen D., Korman, Alan J., Loibner, Hans, Hank, Jacquelyn A., Rakhmilevich, Alexander L., Harari, Paul M., Sondel, Paul M., Huelsmann, Erica, Broucek, Joseph, Brech, Dorothee, Straub, Tobias, Irmler, Martin, Beckers, Johannes, Buettner, Florian, Schaeffeler, Elke, Schwab, Matthias, Noessner, Elfriede, Wolfreys, Alison, Da Costa, Andre, Silva, John, Crosby, Andrea, Staelens, Ludovicus, Craggs, Graham, Cauvin, Annick, Mason, Sean, Paterson, Alison M., Lake, Andrew C., Armet, Caroline M., O’Connor, Rachel W., Hill, Jonathan A., Normant, Emmanuel, Adam, Ammar, Biniszkiewicz, Detlev M., Chappel, Scott C., Palombella, Vito J., Holland, Pamela M., Becker, Annette, Leleti, Manmohan R., Newcomb, Eric, Tan, Joanne B. L., Rapisuwon, Suthee, Radfar, Arash, Gardner, Kellie, Gibney, Geoffrey, Atkins, Michael, Rennier, Keith R., Crowder, Robert, Wang, Ping, Pachynski, Russell K., Carrero, Rosa M. Santana, Rivas, Sarai, Beceren-Braun, Figen, Anthony, Scott, Schluns, Kimberly S., Sawant, Deepali, Chikina, Maria, Yano, Hiroshi, Workman, Creg, Salerno, Elise, Mauldin, Ileana, Deacon, Donna, Shea, Sofia, Pinczewski, Joel, Gajewski, Thomas, Spranger, Stefani, Horton, Brendan, Suzuki, Akiko, Leland, Pamela, Joshi, Bharat H., Puri, Raj K., Sweis, Randy F., Bao, Riyue, Luke, Jason, Theodoraki, Marie-Nicole, Mogundo, Frances-Mary, Won, Haejung, Moreira, Dayson, Gao, Chan, Zhao, Xingli, Duttagupta, Priyanka, Jones, Jeremy, D’Apuzzo, Massimo, and Pal, Sumanta

Subjects
Meeting Abstracts
Published
2016

12. 31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016): part two

Author

Ager, Casey, primary, Reilley, Matthew, additional, Nicholas, Courtney, additional, Bartkowiak, Todd, additional, Jaiswal, Ashvin, additional, Curran, Michael, additional, Albershardt, Tina C., additional, Bajaj, Anshika, additional, Archer, Jacob F., additional, Reeves, Rebecca S., additional, Ngo, Lisa Y., additional, Berglund, Peter, additional, ter Meulen, Jan, additional, Denis, Caroline, additional, Ghadially, Hormas, additional, Arnoux, Thomas, additional, Chanuc, Fabien, additional, Fuseri, Nicolas, additional, Wilkinson, Robert W., additional, Wagtmann, Nicolai, additional, Morel, Yannis, additional, Andre, Pascale, additional, Atkins, Michael B., additional, Carlino, Matteo S., additional, Ribas, Antoni, additional, Thompson, John A., additional, Choueiri, Toni K., additional, Hodi, F. Stephen, additional, Hwu, Wen-Jen, additional, McDermott, David F., additional, Atkinson, Victoria, additional, Cebon, Jonathan S., additional, Fitzharris, Bernie, additional, Jameson, Michael B., additional, McNeil, Catriona, additional, Hill, Andrew G., additional, Mangin, Eric, additional, Ahamadi, Malidi, additional, van Vugt, Marianne, additional, van Zutphen, Mariëlle, additional, Ibrahim, Nageatte, additional, Long, Georgina V., additional, Gartrell, Robyn, additional, Blake, Zoe, additional, Simoes, Ines, additional, Fu, Yichun, additional, Saito, Takuro, additional, Qian, Yingzhi, additional, Lu, Yan, additional, Saenger, Yvonne M., additional, Budhu, Sadna, additional, De Henau, Olivier, additional, Zappasodi, Roberta, additional, Schlunegger, Kyle, additional, Freimark, Bruce, additional, Hutchins, Jeff, additional, Barker, Christopher A., additional, Wolchok, Jedd D., additional, Merghoub, Taha, additional, Burova, Elena, additional, Allbritton, Omaira, additional, Hong, Peter, additional, Dai, Jie, additional, Pei, Jerry, additional, Liu, Matt, additional, Kantrowitz, Joel, additional, Lai, Venus, additional, Poueymirou, William, additional, MacDonald, Douglas, additional, Ioffe, Ella, additional, Mohrs, Markus, additional, Olson, William, additional, Thurston, Gavin, additional, Capasso, Cristian, additional, Frascaro, Federica, additional, Carpi, Sara, additional, Tähtinen, Siri, additional, Feola, Sara, additional, Fusciello, Manlio, additional, Peltonen, Karita, additional, Martins, Beatriz, additional, Sjöberg, Madeleine, additional, Pesonen, Sari, additional, Ranki, Tuuli, additional, Kyruk, Lukasz, additional, Ylösmäki, Erkko, additional, Cerullo, Vincenzo, additional, Cerignoli, Fabio, additional, Xi, Biao, additional, Guenther, Garret, additional, Yu, Naichen, additional, Muir, Lincoln, additional, Zhao, Leyna, additional, Abassi, Yama, additional, Cervera-Carrascón, Víctor, additional, Siurala, Mikko, additional, Santos, João, additional, Havunen, Riikka, additional, Parviainen, Suvi, additional, Hemminki, Akseli, additional, Dalgleish, Angus, additional, Mudan, Satvinder, additional, DeBenedette, Mark, additional, Plachco, Ana, additional, Gamble, Alicia, additional, Grogan, Elizabeth W., additional, Krisko, John, additional, Tcherepanova, Irina, additional, Nicolette, Charles, additional, Dhupkar, Pooja, additional, Yu, Ling, additional, Kleinerman, Eugenie S., additional, Gordon, Nancy, additional, Grenga, Italia, additional, Lepone, Lauren, additional, Gameiro, Sofia, additional, Knudson, Karin M., additional, Fantini, Massimo, additional, Tsang, Kwong, additional, Hodge, James, additional, Donahue, Renee, additional, Schlom, Jeffrey, additional, Evans, Elizabeth, additional, Bussler, Holm, additional, Mallow, Crystal, additional, Reilly, Christine, additional, Torno, Sebold, additional, Scrivens, Maria, additional, Foster, Cathie, additional, Howell, Alan, additional, Balch, Leslie, additional, Knapp, Alyssa, additional, Leonard, John E., additional, Paris, Mark, additional, Fisher, Terry, additional, Hu-Lieskovan, Siwen, additional, Smith, Ernest, additional, Zauderer, Maurice, additional, Fogler, William, additional, Franklin, Marilyn, additional, Thayer, Matt, additional, Saims, Dan, additional, Magnani, John L., additional, Gong, Jian, additional, Gray, Michael, additional, Fromm, George, additional, de Silva, Suresh, additional, Giffin, Louise, additional, Xu, Xin, additional, Rose, Jason, additional, Schreiber, Taylor H., additional, Gameiro, Sofia R., additional, Clavijo, Paul E., additional, Allen, Clint T., additional, Hodge, James W., additional, Tsang, Kwong Y., additional, Grogan, Jane, additional, Manieri, Nicholas, additional, Chiang, Eugene, additional, Caplazi, Patrick, additional, Yadav, Mahesh, additional, Hagner, Patrick, additional, Chiu, Hsiling, additional, Waldman, Michelle, additional, Klippel, Anke, additional, Thakurta, Anjan, additional, Pourdehnad, Michael, additional, Gandhi, Anita, additional, Henrich, Ian, additional, Quick, Laura, additional, Young, Rob, additional, Chou, Margaret, additional, Hotson, Andrew, additional, Willingham, Stephen, additional, Ho, Po, additional, Choy, Carmen, additional, Laport, Ginna, additional, McCaffery, Ian, additional, Miller, Richard, additional, Tipton, Kimberly A., additional, Wong, Kenneth R., additional, Singson, Victoria, additional, Wong, Chihunt, additional, Chan, Chanty, additional, Huang, Yuanhiu, additional, Liu, Shouchun, additional, Richardson, Jennifer H., additional, Kavanaugh, W. Michael, additional, West, James, additional, Irving, Bryan A., additional, Jaini, Ritika, additional, Loya, Matthew, additional, Eng, Charis, additional, Johnson, Melissa L., additional, Adjei, Alex A., additional, Opyrchal, Mateusz, additional, Ramalingam, Suresh, additional, Janne, Pasi A., additional, Dominguez, George, additional, Gabrilovich, Dmitry, additional, de Leon, Laura, additional, Hasapidis, Jeannette, additional, Diede, Scott J., additional, Ordentlich, Peter, additional, Cruickshank, Scott, additional, Meyers, Michael L., additional, Hellmann, Matthew D., additional, Kalinski, Pawel, additional, Zureikat, Amer, additional, Edwards, Robert, additional, Muthuswamy, Ravi, additional, Obermajer, Nataša, additional, Urban, Julie, additional, Butterfield, Lisa H., additional, Gooding, William, additional, Zeh, Herbert, additional, Bartlett, David, additional, Zubkova, Olga, additional, Agapova, Larissa, additional, Kapralova, Marina, additional, Krasovskaia, Liudmila, additional, Ovsepyan, Armen, additional, Lykov, Maxim, additional, Eremeev, Artem, additional, Bokovanov, Vladimir, additional, Grigoryeva, Olga, additional, Karpov, Andrey, additional, Ruchko, Sergey, additional, Shuster, Alexandr, additional, Khalil, Danny N., additional, Campesato, Luis Felipe, additional, Li, Yanyun, additional, Lazorchak, Adam S., additional, Patterson, Troy D., additional, Ding, Yueyun, additional, Sasikumar, Pottayil, additional, Sudarshan, Naremaddepalli, additional, Gowda, Nagaraj, additional, Ramachandra, Raghuveer, additional, Samiulla, Dodheri, additional, Giri, Sanjeev, additional, Eswarappa, Rajesh, additional, Ramachandra, Murali, additional, Tuck, David, additional, Wyant, Timothy, additional, Leshem, Jasmin, additional, Liu, Xiu-fen, additional, Bera, Tapan, additional, Terabe, Masaki, additional, Bossenmaier, Birgit, additional, Niederfellner, Gerhard, additional, Reiter, Yoram, additional, Pastan, Ira, additional, Xia, Leiming, additional, Xia, Yang, additional, Hu, Yangyang, additional, Wang, Yi, additional, Bao, Yangyi, additional, Dai, Fu, additional, Huang, Shiang, additional, Hurt, Elaine, additional, Hollingsworth, Robert E., additional, Lum, Lawrence G., additional, Chang, Alfred E., additional, Wicha, Max S., additional, Li, Qiao, additional, Mace, Thomas, additional, Makhijani, Neil, additional, Talbert, Erin, additional, Young, Gregory, additional, Guttridge, Denis, additional, Conwell, Darwin, additional, Lesinski, Gregory B., additional, Gonzales, Rodney JM Macedo, additional, Huffman, Austin P., additional, Wang, Ximi K., additional, Reshef, Ran, additional, MacKinnon, Andy, additional, Chen, Jason, additional, Gross, Matt, additional, Marguier, Gisele, additional, Shwonek, Peter, additional, Sotirovska, Natalija, additional, Steggerda, Susanne, additional, Parlati, Francesco, additional, Makkouk, Amani, additional, Bennett, Mark K., additional, Emberley, Ethan, additional, Huang, Tony, additional, Li, Weiqun, additional, Neou, Silinda, additional, Pan, Alison, additional, Zhang, Jing, additional, Zhang, Winter, additional, Marshall, Netonia, additional, Marron, Thomas U., additional, Agudo, Judith, additional, Brown, Brian, additional, Brody, Joshua, additional, McQuinn, Christopher, additional, Farren, Matthew, additional, Komar, Hannah, additional, Shakya, Reena, additional, Ludwug, Thomas, additional, Morillon, Y. Maurice, additional, Hammond, Scott A., additional, Greiner, John W., additional, Nath, Pulak R., additional, Schwartz, Anthony L., additional, Maric, Dragan, additional, Roberts, David D., additional, Naing, Aung, additional, Papadopoulos, Kyriakos P., additional, Autio, Karen A., additional, Wong, Deborah J., additional, Patel, Manish, additional, Falchook, Gerald, additional, Pant, Shubham, additional, Ott, Patrick A., additional, Whiteside, Melinda, additional, Patnaik, Amita, additional, Mumm, John, additional, Janku, Filip, additional, Chan, Ivan, additional, Bauer, Todd, additional, Colen, Rivka, additional, VanVlasselaer, Peter, additional, Brown, Gail L., additional, Tannir, Nizar M., additional, Oft, Martin, additional, Infante, Jeffrey, additional, Lipson, Evan, additional, Gopal, Ajay, additional, Neelapu, Sattva S., additional, Armand, Philippe, additional, Spurgeon, Stephen, additional, Leonard, John P., additional, Sanborn, Rachel E., additional, Melero, Ignacio, additional, Gajewski, Thomas F., additional, Maurer, Matthew, additional, Perna, Serena, additional, Gutierrez, Andres A., additional, Clynes, Raphael, additional, Mitra, Priyam, additional, Suryawanshi, Satyendra, additional, Gladstone, Douglas, additional, Callahan, Margaret K., additional, Crooks, James, additional, Brown, Sheila, additional, Gauthier, Audrey, additional, de Boisferon, Marc Hillairet, additional, MacDonald, Andrew, additional, Brunet, Laura Rosa, additional, Rothwell, William T., additional, Bell, Peter, additional, Wilson, James M., additional, Sato-Kaneko, Fumi, additional, Yao, Shiyin, additional, Zhang, Shannon S., additional, Carson, Dennis A., additional, Guiducci, Cristina, additional, Coffman, Robert L., additional, Kitaura, Kazutaka, additional, Matsutani, Takaji, additional, Suzuki, Ryuji, additional, Hayashi, Tomoko, additional, Cohen, Ezra E. W., additional, Schaer, David, additional, Li, Yanxia, additional, Dobkin, Julie, additional, Amatulli, Michael, additional, Hall, Gerald, additional, Doman, Thompson, additional, Manro, Jason, additional, Dorsey, Frank Charles, additional, Sams, Lillian, additional, Holmgaard, Rikke, additional, Persaud, Krishnadatt, additional, Ludwig, Dale, additional, Surguladze, David, additional, Kauh, John S., additional, Novosiadly, Ruslan, additional, Kalos, Michael, additional, Driscoll, Kyla, additional, Pandha, Hardev, additional, Ralph, Christy, additional, Harrington, Kevin, additional, Curti, Brendan, additional, Akerley, Wallace, additional, Gupta, Sumati, additional, Melcher, Alan, additional, Mansfield, David, additional, Kaufman, David R., additional, Schmidt, Emmett, additional, Grose, Mark, additional, Davies, Bronwyn, additional, Karpathy, Roberta, additional, Shafren, Darren, additional, Shamalov, Katerina, additional, Cohen, Cyrille, additional, Sharma, Naveen, additional, Allison, James, additional, Shekarian, Tala, additional, Valsesia-Wittmann, Sandrine, additional, Caux, Christophe, additional, Marabelle, Aurelien, additional, Slomovitz, Brian M., additional, Moore, Kathleen M., additional, Youssoufian, Hagop, additional, Posner, Marshall, additional, Tewary, Poonam, additional, Brooks, Alan D., additional, Xu, Ya-Ming, additional, Wijeratne, Kithsiri, additional, Gunatilaka, Leslie A. A., additional, Sayers, Thomas J., additional, Vasilakos, John P., additional, Alston, Tesha, additional, Dovedi, Simon, additional, Elvecrog, James, additional, Grigsby, Iwen, additional, Herbst, Ronald, additional, Johnson, Karen, additional, Moeckly, Craig, additional, Mullins, Stefanie, additional, Siebenaler, Kristen, additional, SternJohn, Julius, additional, Tilahun, Ashenafi, additional, Tomai, Mark A., additional, Vogel, Katharina, additional, Vietsch, Eveline E., additional, Wellstein, Anton, additional, Wythes, Martin, additional, Crosignani, Stefano, additional, Tumang, Joseph, additional, Alekar, Shilpa, additional, Bingham, Patrick, additional, Cauwenberghs, Sandra, additional, Chaplin, Jenny, additional, Dalvie, Deepak, additional, Denies, Sofie, additional, De Maeseneire, Coraline, additional, Feng, JunLi, additional, Frederix, Kim, additional, Greasley, Samantha, additional, Guo, Jie, additional, Hardwick, James, additional, Kaiser, Stephen, additional, Jessen, Katti, additional, Kindt, Erick, additional, Letellier, Marie-Claire, additional, Li, Wenlin, additional, Maegley, Karen, additional, Marillier, Reece, additional, Miller, Nichol, additional, Murray, Brion, additional, Pirson, Romain, additional, Preillon, Julie, additional, Rabolli, Virginie, additional, Ray, Chad, additional, Ryan, Kevin, additional, Scales, Stephanie, additional, Srirangam, Jay, additional, Solowiej, Jim, additional, Stewart, Al, additional, Streiner, Nicole, additional, Torti, Vince, additional, Tsaparikos, Konstantinos, additional, Zheng, Xianxian, additional, Driessens, Gregory, additional, Gomes, Bruno, additional, Kraus, Manfred, additional, Xu, Chunxiao, additional, Zhang, Yanping, additional, Kradjian, Giorgio, additional, Qin, Guozhong, additional, Qi, Jin, additional, Xu, Xiaomei, additional, Marelli, Bo, additional, Yu, Huakui, additional, Guzman, Wilson, additional, Tighe, Rober, additional, Salazar, Rachel, additional, Lo, Kin-Ming, additional, English, Jessie, additional, Radvanyi, Laszlo, additional, Lan, Yan, additional, Postow, Michael, additional, Senbabaoglu, Yasin, additional, Gasmi, Billel, additional, Zhong, Hong, additional, Liu, Cailian, additional, Hirschhorhn-Cymerman, Daniel, additional, Zha, Yuanyuan, additional, Malnassy, Gregory, additional, Fulton, Noreen, additional, Park, Jae-Hyun, additional, Stock, Wendy, additional, Nakamura, Yusuke, additional, Liu, Hongtao, additional, Ju, Xiaoming, additional, Kosoff, Rachelle, additional, Ramos, Kimberly, additional, Coder, Brandon, additional, Petit, Robert, additional, Princiotta, Michael, additional, Perry, Kyle, additional, Zou, Jun, additional, Arina, Ainhoa, additional, Fernandez, Christian, additional, Zheng, Wenxin, additional, Beckett, Michael A., additional, Mauceri, Helena J., additional, Fu, Yang-Xin, additional, Weichselbaum, Ralph R., additional, Lewis, Whitney, additional, Han, Yanyan, additional, Wu, Yeting, additional, Yang, Chou, additional, Huang, Jing, additional, Wu, Dongyun, additional, Li, Jin, additional, Liang, Xiaoling, additional, Zhou, Xiangjun, additional, Hou, Jinlin, additional, Hassan, Raffit, additional, Jahan, Thierry, additional, Antonia, Scott J., additional, Kindler, Hedy L., additional, Alley, Evan W., additional, Honarmand, Somayeh, additional, Liu, Weiqun, additional, Leong, Meredith L., additional, Whiting, Chan C., additional, Nair, Nitya, additional, Enstrom, Amanda, additional, Lemmens, Edward E., additional, Tsujikawa, Takahiro, additional, Kumar, Sushil, additional, Coussens, Lisa M., additional, Murphy, Aimee L., additional, Brockstedt, Dirk G., additional, Koch, Sven D., additional, Sebastian, Martin, additional, Weiss, Christian, additional, Früh, Martin, additional, Pless, Miklos, additional, Cathomas, Richard, additional, Hilbe, Wolfgang, additional, Pall, Georg, additional, Wehler, Thomas, additional, Alt, Jürgen, additional, Bischoff, Helge, additional, Geissler, Michael, additional, Griesinger, Frank, additional, Kollmeier, Jens, additional, Papachristofilou, Alexandros, additional, Doener, Fatma, additional, Fotin-Mleczek, Mariola, additional, Hipp, Madeleine, additional, Hong, Henoch S., additional, Kallen, Karl-Josef, additional, Klinkhardt, Ute, additional, Stosnach, Claudia, additional, Scheel, Birgit, additional, Schroeder, Andreas, additional, Seibel, Tobias, additional, Gnad-Vogt, Ulrike, additional, Zippelius, Alfred, additional, Park, Ha-Ram, additional, Ahn, Yong-Oon, additional, Kim, Tae Min, additional, Kim, Soyeon, additional, Kim, Seulki, additional, Lee, Yu Soo, additional, Keam, Bhumsuk, additional, Kim, Dong-Wan, additional, Heo, Dae Seog, additional, Pilon-Thomas, Shari, additional, Weber, Amy, additional, Morse, Jennifer, additional, Kodumudi, Krithika, additional, Liu, Hao, additional, Mullinax, John, additional, Sarnaik, Amod A., additional, Pike, Luke, additional, Bang, Andrew, additional, Balboni, Tracy, additional, Taylor, Allison, additional, Spektor, Alexander, additional, Wilhite, Tyler, additional, Krishnan, Monica, additional, Cagney, Daniel, additional, Alexander, Brian, additional, Aizer, Ayal, additional, Buchbinder, Elizabeth, additional, Awad, Mark, additional, Ghandi, Leena, additional, Schoenfeld, Jonathan, additional, Lessey-Morillon, Elizabeth, additional, Ridnour, Lisa, additional, Segal, Neil H., additional, Sharma, Manish, additional, Le, Dung T., additional, Ferris, Robert L., additional, Zelenetz, Andrew D., additional, Levy, Ronald, additional, Lossos, Izidore S., additional, Jacobson, Caron, additional, Ramchandren, Radhakrishnan, additional, Godwin, John, additional, Colevas, A. Dimitrios, additional, Meier, Roland, additional, Krishnan, Suba, additional, Gu, Xuemin, additional, Neely, Jaclyn, additional, Timmerman, John, additional, Vanpouille-Box, Claire I., additional, Formenti, Silvia C., additional, Demaria, Sandra, additional, Wennerberg, Erik, additional, Mediero, Aranzazu, additional, Cronstein, Bruce N., additional, Gustafson, Michael P., additional, DiCostanzo, AriCeli, additional, Wheatley, Courtney, additional, Kim, Chul-Ho, additional, Bornschlegl, Svetlana, additional, Gastineau, Dennis A., additional, Johnson, Bruce D., additional, Dietz, Allan B., additional, MacDonald, Cameron, additional, Bucsek, Mark, additional, Qiao, Guanxi, additional, Hylander, Bonnie, additional, Repasky, Elizabeth, additional, Turbitt, William J., additional, Xu, Yitong, additional, Mastro, Andrea, additional, Rogers, Connie J., additional, Withers, Sita, additional, Wang, Ziming, additional, Khuat, Lam T., additional, Dunai, Cordelia, additional, Blazar, Bruce R., additional, Longo, Dan, additional, Rebhun, Robert, additional, Grossenbacher, Steven K., additional, Monjazeb, Arta, additional, Murphy, William J., additional, Rowlinson, Scott, additional, Agnello, Giulia, additional, Alters, Susan, additional, Lowe, David, additional, Scharping, Nicole, additional, Menk, Ashley V., additional, Whetstone, Ryan, additional, Zeng, Xue, additional, Delgoffe, Greg M., additional, Santos, Patricia M., additional, Shi, Jian, additional, Delgoffe, Greg, additional, Nagasaka, Misako, additional, Sukari, Ammar, additional, Byrne-Steele, Miranda, additional, Pan, Wenjing, additional, Hou, Xiaohong, additional, Brown, Brittany, additional, Eisenhower, Mary, additional, Han, Jian, additional, Collins, Natalie, additional, Manguso, Robert, additional, Pope, Hans, additional, Shrestha, Yashaswi, additional, Boehm, Jesse, additional, Haining, W. Nicholas, additional, Cron, Kyle R., additional, Sivan, Ayelet, additional, Aquino-Michaels, Keston, additional, Orecchioni, Marco, additional, Bedognetti, Davide, additional, Hendrickx, Wouter, additional, Fuoco, Claudia, additional, Spada, Filomena, additional, Sgarrella, Francesco, additional, Cesareni, Gianni, additional, Marincola, Francesco, additional, Kostarelos, Kostas, additional, Bianco, Alberto, additional, Delogu, Lucia, additional, Roelands, Jessica, additional, Boughorbel, Sabri, additional, Decock, Julie, additional, Presnell, Scott, additional, Wang, Ena, additional, Marincola, Franco M., additional, Kuppen, Peter, additional, Ceccarelli, Michele, additional, Rinchai, Darawan, additional, Chaussabel, Damien, additional, Miller, Lance, additional, Nguyen, Andrew, additional, Sanborn, J. Zachary, additional, Vaske, Charles, additional, Rabizadeh, Shahrooz, additional, Niazi, Kayvan, additional, Benz, Steven, additional, Patel, Shashank, additional, Restifo, Nicholas, additional, White, James, additional, Angiuoli, Sam, additional, Sausen, Mark, additional, Jones, Sian, additional, Sevdali, Maria, additional, Simmons, John, additional, Velculescu, Victor, additional, Diaz, Luis, additional, Zhang, Theresa, additional, Sims, Jennifer S., additional, Barton, Sunjay M., additional, Kadenhe-Chiweshe, Angela, additional, Dela Cruz, Filemon, additional, Turk, Andrew T., additional, Mazzeo, Christopher F., additional, Kung, Andrew L., additional, Bruce, Jeffrey N., additional, Yamashiro, Darrell J., additional, Connolly, Eileen P., additional, Baird, Jason, additional, Crittenden, Marka, additional, Friedman, David, additional, Xiao, Hong, additional, Leidner, Rom, additional, Bell, Bryan, additional, Young, Kristina, additional, Gough, Michael, additional, Bian, Zhen, additional, Kidder, Koby, additional, Liu, Yuan, additional, Curran, Emily, additional, Chen, Xiufen, additional, Corrales, Leticia P., additional, Kline, Justin, additional, Aguilar, Ethan G., additional, Guerriero, Jennifer, additional, Sotayo, Alaba, additional, Ponichtera, Holly, additional, Pourzia, Alexandra, additional, Schad, Sara, additional, Carrasco, Ruben, additional, Lazo, Suzan, additional, Bronson, Roderick, additional, Letai, Anthony, additional, Kornbluth, Richard S., additional, Gupta, Sachin, additional, Termini, James, additional, Guirado, Elizabeth, additional, Stone, Geoffrey W., additional, Meyer, Christina, additional, Helming, Laura, additional, Wilson, Nicholas, additional, Hofmeister, Robert, additional, Neubert, Natalie J., additional, Tillé, Laure, additional, Barras, David, additional, Soneson, Charlotte, additional, Baumgaertner, Petra, additional, Rimoldi, Donata, additional, Gfeller, David, additional, Delorenzi, Mauro, additional, Fuertes Marraco, Silvia A., additional, Speiser, Daniel E., additional, Abraham, Tara S., additional, Xiang, Bo, additional, Magee, Michael S., additional, Waldman, Scott A., additional, Snook, Adam E., additional, Blogowski, Wojciech, additional, Zuba-Surma, Ewa, additional, Budkowska, Marta, additional, Salata, Daria, additional, Dolegowska, Barbara, additional, Starzynska, Teresa, additional, Chan, Leo, additional, Somanchi, Srinivas, additional, McCulley, Kelsey, additional, Lee, Dean, additional, Buettner, Nico, additional, Shi, Feng, additional, Myers, Paisley T., additional, Curbishley, Stuart, additional, Penny, Sarah A., additional, Steadman, Lora, additional, Millar, David, additional, Speers, Ellen, additional, Ruth, Nicola, additional, Wong, Gabriel, additional, Thimme, Robert, additional, Adams, David, additional, Cobbold, Mark, additional, Thomas, Remy, additional, Al-Muftah, Mariam, additional, Wong, Michael KK, additional, Morse, Michael, additional, Clark, Joseph I., additional, Kaufman, Howard L., additional, Daniels, Gregory A., additional, Hua, Hong, additional, Rao, Tharak, additional, Dutcher, Janice P., additional, Kang, Kai, additional, Saunthararajah, Yogen, additional, Velcheti, Vamsidhar, additional, Kumar, Vikas, additional, Anwar, Firoz, additional, Verma, Amita, additional, Chheda, Zinal, additional, Kohanbash, Gary, additional, Sidney, John, additional, Okada, Kaori, additional, Shrivastav, Shruti, additional, Carrera, Diego A., additional, Liu, Shuming, additional, Jahan, Naznin, additional, Mueller, Sabine, additional, Pollack, Ian F., additional, Carcaboso, Angel M., additional, Sette, Alessandro, additional, Hou, Yafei, additional, Okada, Hideho, additional, Field, Jessica J., additional, Zeng, Weiping, additional, Shih, Vincent FS, additional, Law, Che-Leung, additional, Senter, Peter D., additional, Gardai, Shyra J., additional, Okeley, Nicole M., additional, Abelin, Jennifer G., additional, Saeed, Abu Z., additional, Malaker, Stacy A., additional, Shabanowitz, Jeffrey, additional, Ward, Stephen T., additional, Hunt, Donald F., additional, Profusek, Pam, additional, Wood, Laura, additional, Shepard, Dale, additional, Grivas, Petros, additional, Kapp, Kerstin, additional, Volz, Barbara, additional, Oswald, Detlef, additional, Wittig, Burghardt, additional, Schmidt, Manuel, additional, Sefrin, Julian P., additional, Hillringhaus, Lars, additional, Lifke, Valeria, additional, Lifke, Alexander, additional, Skaletskaya, Anna, additional, Ponte, Jose, additional, Chittenden, Thomas, additional, Setiady, Yulius, additional, Sivado, Eva, additional, Thomas, Vincent, additional, El Alaoui, Meddy, additional, Papot, Sébastien, additional, Dumontet, Charles, additional, Dyson, Mike, additional, McCafferty, John, additional, El Alaoui, Said, additional, Bommareddy, Praveen K., additional, Zloza, Andrew, additional, Kohlhapp, Frederick, additional, Silk, Ann W., additional, Jhawar, Sachin, additional, Paneque, Tomas, additional, Newman, Jenna, additional, Beltran, Pedro, additional, Cao, Felicia, additional, Hong, Bang-Xing, additional, Rodriguez-Cruz, Tania, additional, Song, Xiao-Tong, additional, Gottschalk, Stephen, additional, Calderon, Hugo, additional, Illingworth, Sam, additional, Brown, Alice, additional, Fisher, Kerry, additional, Seymour, Len, additional, Champion, Brian, additional, Eriksson, Emma, additional, Wenthe, Jessica, additional, Hellström, Ann-Charlotte, additional, Paul-Wetterberg, Gabriella, additional, Loskog, Angelica, additional, Milenova, Ioanna, additional, Ståhle, Magnus, additional, Jarblad-Leja, Justyna, additional, Ullenhag, Gustav, additional, Dimberg, Anna, additional, Moreno, Rafael, additional, Alemany, Ramon, additional, Goyal, Sharad, additional, Silk, Ann, additional, Mehnert, Janice, additional, Gabrail, Nashat, additional, Bryan, Jennifer, additional, Medina, Daniel, additional, Mitchell, Leah, additional, Yagiz, Kader, additional, Lopez, Fernando, additional, Mendoza, Daniel, additional, Munday, Anthony, additional, Gruber, Harry, additional, Jolly, Douglas, additional, Fuhrmann, Steven, additional, Radoja, Sasa, additional, Tan, Wei, additional, Pourchet, Aldo, additional, Frey, Alan, additional, Mohr, Ian, additional, Mulvey, Matthew, additional, Andtbacka, Robert H. I., additional, Ross, Merrick, additional, Agarwala, Sanjiv, additional, Grossmann, Kenneth, additional, Taylor, Matthew, additional, Vetto, John, additional, Neves, Rogerio, additional, Daud, Adil, additional, Khong, Hung, additional, Meek, Stephanie M., additional, Ungerleider, Richard, additional, Welden, Scott, additional, Tanaka, Maki, additional, Williams, Matthew, additional, Hallmeyer, Sigrun, additional, Fox, Bernard, additional, Feng, Zipei, additional, Paustian, Christopher, additional, Bifulco, Carlo, additional, Zafar, Sadia, additional, Hemminki, Otto, additional, Bramante, Simona, additional, Vassilev, Lotta, additional, Wang, Hongjie, additional, Lieber, Andre, additional, Hemmi, Silvio, additional, de Gruijl, Tanja, additional, Kanerva, Anna, additional, Ansari, Tameem, additional, Sundararaman, Srividya, additional, Roen, Diana, additional, Lehmann, Paul, additional, Bloom, Anja C., additional, Bender, Lewis H., additional, Walters, Ian B., additional, Berzofsky, Jay A., additional, Chapelin, Fanny, additional, Ahrens, Eric T., additional, DeFalco, Jeff, additional, Harbell, Michael, additional, Manning-Bog, Amy, additional, Scholz, Alexander, additional, Zhang, Danhui, additional, Baia, Gilson, additional, Tan, Yann Chong, additional, Sokolove, Jeremy, additional, Kim, Dongkyoon, additional, Williamson, Kevin, additional, Chen, Xiaomu, additional, Colrain, Jillian, additional, Santo, Gregg Espiritu, additional, Nguyen, Ngan, additional, Volkmuth, Wayne, additional, Greenberg, Norman, additional, Robinson, William, additional, Emerling, Daniel, additional, Drake, Charles G., additional, Petrylak, Daniel P., additional, Antonarakis, Emmanuel S., additional, Kibel, Adam S., additional, Chang, Nancy N., additional, Vu, Tuyen, additional, Campogan, Dwayne, additional, Haynes, Heather, additional, Trager, James B., additional, Sheikh, Nadeem A., additional, Quinn, David I., additional, Kirk, Peter, additional, Addepalli, Murali, additional, Chang, Thomas, additional, Zhang, Ping, additional, Konakova, Marina, additional, Hagihara, Katsunobu, additional, Pai, Steven, additional, VanderVeen, Laurie, additional, Obalapur, Palakshi, additional, Kuo, Peiwen, additional, Quach, Phi, additional, Fong, Lawrence, additional, Charych, Deborah H., additional, Zalevsky, Jonathan, additional, Langowski, John L., additional, Kirksey, Yolanda, additional, Nutakki, Ravi, additional, Kolarkar, Shalini, additional, Pena, Rhoneil, additional, Hoch, Ute, additional, Doberstein, Stephen K., additional, Cha, John, additional, Mallon, Zach, additional, Perez, Myra, additional, McDaniel, Amanda, additional, Anand, Snjezana, additional, Uecker, Darrin, additional, Nuccitelli, Richard, additional, Wieckowski, Eva, additional, Muthuswamy, Ravikumar, additional, Ravindranathan, Roshni, additional, Renrick, Ariana N., additional, Thounaojam, Menaka, additional, Thomas, Portia, additional, Pellom, Samuel, additional, Shanker, Anil, additional, Dudimah, Duafalia, additional, Brooks, Alan, additional, Su, Yu-Lin, additional, Adamus, Tomasz, additional, Zhang, Qifang, additional, Nechaev, Sergey, additional, Kortylewski, Marcin, additional, Wei, Spencer, additional, Anderson, Clark, additional, Tang, Chad, additional, Schoenhals, Jonathan, additional, Tsouko, Efrosini, additional, Heymach, John, additional, de Groot, Patricia, additional, Chang, Joe, additional, Hess, Kenneth R., additional, Diab, Adi, additional, Sharma, Padmanee, additional, Hong, David, additional, Welsh, James, additional, Parsons, Andrea J., additional, Leleux, Jardin, additional, Ascarateil, Stephane, additional, Koziol, Marie Eve, additional, Bai, Dina, additional, Dai, Peihong, additional, Wang, Weiyi, additional, Yang, Ning, additional, Shuman, Stewart, additional, Deng, Liang, additional, Dillon, Patrick, additional, Petroni, Gina, additional, Brenin, David, additional, Bullock, Kim, additional, Olson, Walter, additional, Smolkin, Mark E., additional, Smith, Kelly, additional, Nail, Carmel, additional, Slingluff, Craig L., additional, Sharma, Meenu, additional, Fa’ak, Faisal, additional, Janssen, Louise, additional, Khong, Hiep, additional, Xiao, Zhilan, additional, Hailemichael, Yared, additional, Singh, Manisha, additional, Vianden, Christina, additional, Overwijk, Willem W., additional, Facciabene, Andrea, additional, Stefano, Pierini, additional, Chongyung, Fang, additional, Rafail, Stavros, additional, Nielsen, Michael, additional, Vanderslice, Peter, additional, Woodside, Darren G., additional, Market, Robert V., additional, Biediger, Ronald J., additional, Marathi, Upendra K., additional, Hollevoet, Kevin, additional, Geukens, Nick, additional, Declerck, Paul, additional, Joly, Nathalie, additional, McIntosh, Laura, additional, Paramithiotis, Eustache, additional, Rizell, Magnus, additional, Sternby, Malin, additional, Andersson, Bengt, additional, Karlsson-Parra, Alex, additional, Kuai, Rui, additional, Ochyl, Lukasz, additional, Schwendeman, Anna, additional, Moon, James, additional, Deng, Weiwen, additional, Hudson, Thomas E., additional, Hanson, Bill, additional, Rae, Chris S., additional, Burrill, Joel, additional, Skoble, Justin, additional, Katibah, George, additional, deVries, Michele, additional, Lauer, Peter, additional, Dubensky, Thomas W., additional, Chen, Xin, additional, Zhou, Li, additional, Ren, Xiubao, additional, Aggarwal, Charu, additional, Mangrolia, Drishty, additional, Cohen, Roger, additional, Weinstein, Gregory, additional, Morrow, Matthew, additional, Bauml, Joshua, additional, Kraynyak, Kim, additional, Boyer, Jean, additional, Yan, Jian, additional, Lee, Jessica, additional, Humeau, Laurent, additional, Oyola, Sandra, additional, Duff, Susan, additional, Weiner, David, additional, Yang, Zane, additional, Bagarazzi, Mark, additional, McNeel, Douglas G., additional, Eickhoff, Jens, additional, Jeraj, Robert, additional, Staab, Mary Jane, additional, Straus, Jane, additional, Rekoske, Brian, additional, Liu, Glenn, additional, Melssen, Marit, additional, Grosh, William, additional, Varhegyi, Nikole, additional, Galeassi, Nadejda, additional, Deacon, Donna H., additional, Gaughan, Elizabeth, additional, Ghisoli, Maurizio, additional, Barve, Minal, additional, Mennel, Robert, additional, Wallraven, Gladice, additional, Manning, Luisa, additional, Senzer, Neil, additional, Nemunaitis, John, additional, Ogasawara, Masahiro, additional, Ota, Shuichi, additional, Peace, Kaitlin M., additional, Hale, Diane F., additional, Vreeland, Timothy J., additional, Jackson, Doreen O., additional, Berry, John S., additional, Trappey, Alfred F., additional, Herbert, Garth S., additional, Clifton, Guy T., additional, Hardin, Mark O., additional, Toms, Anne, additional, Qiao, Na, additional, Litton, Jennifer, additional, Peoples, George E., additional, Mittendorf, Elizabeth A., additional, Ghamsari, Lila, additional, Flano, Emilio, additional, Jacques, Judy, additional, Liu, Biao, additional, Havel, Jonathan, additional, Makarov, Vladimir, additional, Chan, Timothy A., additional, Flechtner, Jessica B., additional, Facciponte, John, additional, Ugel, Stefano, additional, De Sanctis, Francesco, additional, Coukos, George, additional, Paris, Sébastien, additional, Pottier, Agnes, additional, Levy, Laurent, additional, Lu, Bo, additional, Cappuccini, Federica, additional, Pollock, Emily, additional, Bryant, Richard, additional, Hamdy, Freddie, additional, Hill, Adrian, additional, Redchenko, Irina, additional, Sultan, Hussein, additional, Kumai, Takumi, additional, Fesenkova, Valentyna, additional, Celis, Esteban, additional, Fernando, Ingrid, additional, Palena, Claudia, additional, David, Justin M., additional, Gabitzsch, Elizabeth, additional, Jones, Frank, additional, Gulley, James L., additional, Herranz, Mireia Uribe, additional, Wada, Hiroshi, additional, Shimizu, Atsushi, additional, Osada, Toshihiro, additional, Fukaya, Satoshi, additional, Sasaki, Eiji, additional, Abolhalaj, Milad, additional, Askmyr, David, additional, Lundberg, Kristina, additional, Albrekt, Ann-Sofie, additional, Greiff, Lennart, additional, Lindstedt, Malin, additional, Flies, Dallas B., additional, Higuchi, Tomoe, additional, Ornatowski, Wojciech, additional, Harris, Jaryse, additional, Adams, Sarah F., additional, Aguilera, Todd, additional, Rafat, Marjan, additional, Castellini, Laura, additional, Shehade, Hussein, additional, Kariolis, Mihalis, additional, Jang, Dadi, additional, vonEbyen, Rie, additional, Graves, Edward, additional, Ellies, Lesley, additional, Rankin, Erinn, additional, Koong, Albert, additional, Giaccia, Amato, additional, Ajina, Reham, additional, Wang, Shangzi, additional, Smith, Jill, additional, Pierobon, Mariaelena, additional, Jablonski, Sandra, additional, Petricoin, Emanuel, additional, Weiner, Louis M., additional, Sherry, Lorcan, additional, Waller, John, additional, Anderson, Mark, additional, Bigley, Alison, additional, Bernatchez, Chantale, additional, Haymaker, Cara, additional, Kluger, Harriet, additional, Tetzlaff, Michael, additional, Jackson, Natalie, additional, Gergel, Ivan, additional, Tagliaferri, Mary, additional, Hwu, Patrick, additional, Snzol, Mario, additional, Hurwitz, Michael, additional, Barberi, Theresa, additional, Martin, Allison, additional, Suresh, Rahul, additional, Barakat, David, additional, Harris-Bookman, Sarah, additional, Drake, Charles, additional, Friedman, Alan, additional, Berkey, Sara, additional, Downs-Canner, Stephanie, additional, Edwards, Robert P., additional, Curiel, Tyler, additional, Odunsi, Kunle, additional, Bruno, Tullia C., additional, Moore, Brandon, additional, Squalls, Olivia, additional, Ebner, Peggy, additional, Waugh, Katherine, additional, Mitchell, John, additional, Franklin, Wilbur, additional, Merrick, Daniel, additional, McCarter, Martin, additional, Palmer, Brent, additional, Kern, Jeffrey, additional, Vignali, Dario, additional, Slansky, Jill, additional, Chan, Anissa S. H., additional, Qiu, Xiaohong, additional, Fraser, Kathryn, additional, Jonas, Adria, additional, Ottoson, Nadine, additional, Gordon, Keith, additional, Kangas, Takashi O., additional, Leonardo, Steven, additional, Ertelt, Kathleen, additional, Walsh, Richard, additional, Uhlik, Mark, additional, Graff, Jeremy, additional, Bose, Nandita, additional, Gupta, Ravi, additional, Mandloi, Nitin, additional, Paul, Kiran, additional, Patil, Ashwini, additional, Sathian, Rekha, additional, Mohan, Aparna, additional, Manoharan, Malini, additional, Chaudhuri, Amitabha, additional, Chen, Yu, additional, Lin, Jing, additional, Ye, Yun-bin, additional, Xu, Chun-wei, additional, Chen, Gang, additional, Guo, Zeng-qing, additional, Komarov, Andrey, additional, Chenchik, Alex, additional, Makhanov, Michael, additional, Frangou, Costa, additional, Zheng, Yi, additional, Coltharp, Carla, additional, Unfricht, Darryn, additional, Dilworth, Ryan, additional, Fridman, Leticia, additional, Liu, Linying, additional, Rajopadhye, Milind, additional, Miller, Peter, additional, Concha-Benavente, Fernando, additional, Bauman, Julie, additional, Trivedi, Sumita, additional, Srivastava, Raghvendra, additional, Ohr, James, additional, Heron, Dwight, additional, Duvvuri, Uma, additional, Kim, Seungwon, additional, Torrey, Heather, additional, Mera, Toshi, additional, Okubo, Yoshiaki, additional, Vanamee, Eva, additional, Foster, Rosemary, additional, Faustman, Denise, additional, Stack, Edward, additional, Izaki, Daisuke, additional, Beck, Kristen, additional, Jia, Dan Tong, additional, Armenta, Paul, additional, White-Stern, Ashley, additional, Marks, Douglas, additional, Taback, Bret, additional, Horst, Basil, additional, Glickman, Laura Hix, additional, Kanne, David B., additional, Gauthier, Kelsey S., additional, Desbien, Anthony L., additional, Francica, Brian, additional, Leong, Justin L., additional, Sung, Leonard, additional, Metchette, Ken, additional, Kasibhatla, Shailaja, additional, Pferdekamper, Anne Marie, additional, Zheng, Lianxing, additional, Cho, Charles, additional, Feng, Yan, additional, McKenna, Jeffery M., additional, Tallarico, John, additional, Bender, Steven, additional, Ndubaku, Chudi, additional, McWhirter, Sarah M., additional, Gugel, Elena Gonzalez, additional, Bell, Charles J. M., additional, Munk, Adiel, additional, Muniz, Luciana, additional, Bhardwaj, Nina, additional, Zhao, Fei, additional, Evans, Kathy, additional, Xiao, Christine, additional, Holtzhausen, Alisha, additional, Hanks, Brent A., additional, Scholler, Nathalie, additional, Yin, Catherine, additional, Van der Meijs, Pien, additional, Prantner, Andrew M., additional, Krejsa, Cecile M., additional, Smith, Leia, additional, Johnson, Brian, additional, Branstetter, Daniel, additional, Stein, Paul L., additional, Jaen, Juan C., additional, Tan, Joanne BL, additional, Chen, Ada, additional, Park, Timothy, additional, Powers, Jay P., additional, Sexton, Holly, additional, Xu, Guifen, additional, Young, Steve W., additional, Schindler, Ulrike, additional, Deng, Wentao, additional, Klinke, David John, additional, Komar, Hannah M., additional, Serpa, Gregory, additional, Elnaggar, Omar, additional, Hart, Philip, additional, Schmidt, Carl, additional, Dillhoff, Mary, additional, Jin, Ming, additional, Ostrowski, Michael C., additional, Koti, Madhuri, additional, Au, Katrina, additional, Peterson, Nichole, additional, Truesdell, Peter, additional, Reid-Schachter, Gillian, additional, Graham, Charles, additional, Craig, Andrew, additional, Francis, Julie-Ann, additional, Kotlan, Beatrix, additional, Balatoni, Timea, additional, Farkas, Emil, additional, Toth, Laszlo, additional, Ujhelyi, Mihaly, additional, Savolt, Akos, additional, Doleschall, Zoltan, additional, Horvath, Szabolcs, additional, Eles, Klara, additional, Olasz, Judit, additional, Csuka, Orsolya, additional, Kasler, Miklos, additional, Liszkay, Gabriella, additional, Barnea, Eytan, additional, Blakely, Collin, additional, Flynn, Patrick, additional, Goodman, Reid, additional, Bueno, Raphael, additional, Sugarbaker, David, additional, Jablons, David, additional, Broaddus, V. Courtney, additional, West, Brian, additional, Kunk, Paul R., additional, Obeid, Joseph M., additional, Winters, Kevin, additional, Pramoonjago, Patcharin, additional, Stelow, Edward B., additional, Bauer, Todd W., additional, Rahma, Osama E., additional, Lamble, Adam, additional, Kosaka, Yoko, additional, Huang, Fei, additional, Saser, Kate A., additional, Adams, Homer, additional, Tognon, Christina E., additional, Laderas, Ted, additional, McWeeney, Shannon, additional, Loriaux, Marc, additional, Tyner, Jeffery W., additional, Druker, Brian J., additional, Lind, Evan F., additional, Liu, Zhuqing, additional, Lu, Shanhong, additional, Kane, Lawrence P., additional, Shayan, Gulidanna, additional, Femel, Julia, additional, Lane, Ryan, additional, Booth, Jamie, additional, Lund, Amanda W., additional, Rodriguez, Anthony, additional, Engelhard, Victor H., additional, Metelli, Alessandra, additional, Wu, Bill X., additional, Fugle, Caroline W., additional, Saleh, Rachidi, additional, Sun, Shaoli, additional, Wu, Jennifer, additional, Liu, Bei, additional, Li, Zihai, additional, Morris, Zachary S., additional, Guy, Emily I., additional, Heinze, Clinton, additional, Kler, Jasdeep, additional, Gressett, Monica M., additional, Werner, Lauryn R., additional, Gillies, Stephen D., additional, Korman, Alan J., additional, Loibner, Hans, additional, Hank, Jacquelyn A., additional, Rakhmilevich, Alexander L., additional, Harari, Paul M., additional, Sondel, Paul M., additional, Huelsmann, Erica, additional, Broucek, Joseph, additional, Brech, Dorothee, additional, Straub, Tobias, additional, Irmler, Martin, additional, Beckers, Johannes, additional, Buettner, Florian, additional, Schaeffeler, Elke, additional, Schwab, Matthias, additional, Noessner, Elfriede, additional, Wolfreys, Alison, additional, Da Costa, Andre, additional, Silva, John, additional, Crosby, Andrea, additional, Staelens, Ludovicus, additional, Craggs, Graham, additional, Cauvin, Annick, additional, Mason, Sean, additional, Paterson, Alison M., additional, Lake, Andrew C., additional, Armet, Caroline M., additional, O’Connor, Rachel W., additional, Hill, Jonathan A., additional, Normant, Emmanuel, additional, Adam, Ammar, additional, Biniszkiewicz, Detlev M., additional, Chappel, Scott C., additional, Palombella, Vito J., additional, Holland, Pamela M., additional, Becker, Annette, additional, Leleti, Manmohan R., additional, Newcomb, Eric, additional, Tan, Joanne B. L., additional, Rapisuwon, Suthee, additional, Radfar, Arash, additional, Gardner, Kellie, additional, Gibney, Geoffrey, additional, Atkins, Michael, additional, Rennier, Keith R., additional, Crowder, Robert, additional, Wang, Ping, additional, Pachynski, Russell K., additional, Carrero, Rosa M. Santana, additional, Rivas, Sarai, additional, Beceren-Braun, Figen, additional, Anthony, Scott, additional, Schluns, Kimberly S., additional, Sawant, Deepali, additional, Chikina, Maria, additional, Yano, Hiroshi, additional, Workman, Creg, additional, Salerno, Elise, additional, Mauldin, Ileana, additional, Deacon, Donna, additional, Shea, Sofia, additional, Pinczewski, Joel, additional, Gajewski, Thomas, additional, Spranger, Stefani, additional, Horton, Brendan, additional, Suzuki, Akiko, additional, Leland, Pamela, additional, Joshi, Bharat H., additional, Puri, Raj K., additional, Sweis, Randy F., additional, Bao, Riyue, additional, Luke, Jason, additional, Theodoraki, Marie-Nicole, additional, Mogundo, Frances-Mary, additional, Won, Haejung, additional, Moreira, Dayson, additional, Gao, Chan, additional, Zhao, Xingli, additional, Duttagupta, Priyanka, additional, Jones, Jeremy, additional, D’Apuzzo, Massimo, additional, and Pal, Sumanta, additional

Published
2016
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19. Genetic Ablation of Pannexin 1 Protects Retinal Neurons from Ischemic Injury.

Author

Dvoriantchikova, Galina, Ivanov, Dmitry, Barakat, David, Grinberg, Alexander, Wen, Rong, Slepak, Vladlen Z., and Shestopalov, Valery I.

Subjects
GENETICS, ABLATION techniques, NEURONS, ISCHEMIA, RETINAL ganglion cells
Abstract

Pannexin1 (Panx1) forms large nonselective membrane channel that is implicated in paracrine and inflammatory signaling. In vitro experiments suggested that Panx1 could play a key role in ischemic death of hippocampal neurons. Since retinal ganglion cells (RGCs) express high levels of Panx1 and are susceptible to ischemic induced injury, we hypothesized that Panx1 contributes to rapid and selective loss of these neurons in ischemia. To test this hypothesis, we induced experimental retinal ischemia followed by reperfusion in live animals with the Panx1 channel genetically ablated either in the entire mouse (Panx1 KO), or only in neurons using the conditional knockout (Panx1 CKO) technology. Here we report that two distinct neurotoxic processes are induced in RGCs by ischemia in the wild type mice but are inactivated in Panx1KO and Panx1 CKO animals. First, the post-ischemic permeation of RGC plasma membranes is suppressed, as assessed by dye transfer and calcium imaging assays ex vivo and in vitro. Second, the inflammasome-mediated activation of caspase-1 and the production of interleukin-1β in the Panx1 KO retinas are inhibited. Our findings indicate that post-ischemic neurotoxicity in the retina is mediated by previously uncharacterized pathways, which involve neuronal Panx1 and are intrinsic to RGCs. Thus, our work presents the in vivo evidence for neurotoxicity elicited by neuronal Panx1, and identifies this channel as a new therapeutic target in ischemic pathologies. [ABSTRACT FROM AUTHOR]

Published
2012
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20. Liposome-delivered ATP effectively protects the retina against ischemia-reperfusion injury.

Author

Dvoriantchikova G, Barakat DJ, Hernandez E, Shestopalov VI, and Ivanov D

Subjects
Adenosine Triphosphate pharmacology, Animals, Blood-Retinal Barrier drug effects, Blood-Retinal Barrier metabolism, Blood-Retinal Barrier pathology, Cell Death drug effects, Cell Survival drug effects, Gene Expression Regulation drug effects, Glucose deficiency, Inflammation complications, Inflammation drug therapy, Inflammation genetics, Inflammation pathology, Liposomes, Mice, Mice, Inbred C57BL, Oxygen, Reperfusion Injury complications, Retina drug effects, Retinal Ganglion Cells drug effects, Retinal Ganglion Cells pathology, Retinal Ganglion Cells ultrastructure, Retinal Neurons drug effects, Retinal Neurons metabolism, Retinal Neurons pathology, Adenosine Triphosphate administration & dosage, Adenosine Triphosphate therapeutic use, Reperfusion Injury drug therapy, Reperfusion Injury prevention & control, Retina pathology
Abstract

Purpose: We investigated the effect of ATP (ATP) encapsulated in liposomes (ATP-liposomes) on the level of inflammation and neuronal death in the retina induced by ischemia reperfusion (IR)., Methods: Primary retinal ganglion cells treated with ATP-liposomes, empty liposomes, and phosphate buffer solution (PBS) were deprived of oxygen and glucose (OGD) for 6 h in vitro, in an anaerobic chamber. Plates were assessed for the proportion of necrotic versus apoptotic cells and for cell survival 12 h after OGD. For in vivo experiments, we induced retinal ischemia by unilateral elevation of intraocular pressure for 1 h by direct corneal canulation. Mice were injected with liposomes or PBS 24 h before IR, at the time of surgery, and every 24 h until sacrifice. Transmission electron microscopic analysis was used to identify necrotic and apoptotic cells in ischemic retinas. The changes in expression of pro-inflammatory genes 24 h post reperfusion were assessed by quantitative reverse transcription polymerase chain reaction (RT-PCR). Corresponding changes in protein abundances were analyzed by immunohistochemistry. Cell death was evaluated by direct counting of neurons in the ganglion cell layer (GCL) of flatmounted retinas 7 days post reperfusion., Results: Treatment with ATP-liposomes increases retinal ganglion cell (RGC) survival and decreases necrotic cell death following OGD. Injection of ATP-liposomes markedly decreased necrotic cell death in the GCL following retinal ischemia. The ATP-liposome treatment reduced the expression of pro-inflammatory genes, including that of interleukin 1β (Il1β), interleukin 6 (Il6), tumor necrosis factor (Thf), chemokine (C-C motif) ligand 2 (Ccl2), chemokine (C-C motif) ligand 5 (Ccl5), chemokine (C-X-C motif) ligand 10 (Cxcl10), intercellular adhesion molecule 1 (Icam1), and nitric oxide synthase 2 (Nos2), in the retina 24 h after IR and significantly reduced the GCL neuron death rate 7 days after reperfusion., Conclusions: ATP-liposome treatment of IR-challenged neural tissues suppressed necrosis and correlated with a significantly reduced level of inflammation and retinal damage.

Published
2010

21. Toll-like receptor 4 contributes to retinal ischemia/reperfusion injury.

Author

Dvoriantchikova G, Barakat DJ, Hernandez E, Shestopalov VI, and Ivanov D

Subjects
Animals, Cell Survival, Cytoprotection, Inflammation complications, Inflammation pathology, Inflammation Mediators metabolism, Mice, Mice, Inbred C57BL, Reperfusion Injury complications, Reperfusion Injury pathology, Retinal Neurons metabolism, Retinal Neurons pathology, Signal Transduction, Toll-Like Receptor 4 deficiency, Reperfusion Injury metabolism, Retina metabolism, Retina pathology, Toll-Like Receptor 4 metabolism
Abstract

Purpose: We investigated whether retinal ischemia and inflammation produced by raising the intraocular pressure above normal systolic levels differs in mice that lack a functional toll-like receptor 4 (Tlr4) signaling pathway., Methods: In this work we used the murine strain B6.B10ScN-Tlr4(lps-del)/JthJ, which does not express functional Tlr4. C57BL/6J was considered as the control. We induced retinal ischemia by unilateral elevation of intraocular pressure for 1 h by direct corneal cannulation. The changes in expression of proinflammatory genes 24 h postreperfusion were assessed by quantitative PCR. Corresponding changes in protein abundances were analyzed by western blot and immunohistochemistry. Cell death was evaluated by direct counting of neurons in the ganglion cell layer of flat-mounted retinas seven days postreperfusion., Results: We showed that Tlr4-deficient mice display significantly reduced expression of proinflammatory genes, including RelA, tumor necrosis factor (Thf), interleukin 6 (Il6), chemokine (C-C motif) ligand 2 (Ccl2), chemokine (C-C motif) ligand 5 (Ccl5), chemokine (C-X-C motif) ligand 10 (Cxcl10), Cybb, nitric oxide synthase 2 (Nos2), and intercellular adhesion molecule 1 (Icam1) 24 h after reperfusion. The mice that lacked Tlr4 showed significantly increased survival of neurons in the ganglion cell layer following ischemic injury, as compared to wild-type controls., Conclusions: Our results indicate that Tlr4 signaling is involved in retinal damage and inflammation triggered by ischemic injury.

Published
2010

22. Inactivation of astroglial NF-kappa B promotes survival of retinal neurons following ischemic injury.

Author

Dvoriantchikova G, Barakat D, Brambilla R, Agudelo C, Hernandez E, Bethea JR, Shestopalov VI, and Ivanov D

Subjects
Animals, Cell Survival physiology, Gene Silencing physiology, Ischemia pathology, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, NF-kappa B antagonists & inhibitors, NF-kappa B genetics, Retinal Artery physiology, Retinal Neurons pathology, Astrocytes physiology, Ischemia genetics, Ischemia metabolism, NF-kappa B metabolism, Retinal Neurons physiology
Abstract

Reactive astrocytes have been implicated in neuronal loss following ischemic stroke. However, the molecular mechanisms associated with this process are yet to be fully elucidated. In this work, we tested the hypothesis that astroglial NF-kappaB, a key regulator of inflammatory responses, is a contributor to neuronal death following ischemic injury. We compared neuronal survival in the ganglion cell layer (GCL) after retinal ischemia-reperfusion in wild-type (WT) and in GFAP-IkappaBalpha-dn transgenic mice, where the NF-kappaB classical pathway is suppressed specifically in astrocytes. The GFAP-IkappaBalpha-dn mice showed significantly increased survival of neurons in the GCL following ischemic injury as compared with WT littermates. Neuroprotection was associated with significantly reduced expression of pro-inflammatory genes, encoding Tnf-alpha, Ccl2 (Mcp1), Cxcl10 (IP10), Icam1, Vcam1, several subunits of NADPH oxidase and NO-synthase in the retinas of GFAP-IkappaBalpha-dn mice. These data suggest that certain NF-kappaB-regulated pro-inflammatory and redox-active pathways are central to glial neurotoxicity induced by ischemic injury. The inhibition of these pathways in astrocytes may represent a feasible neuroprotective strategy for retinal ischemia and stroke.

Published
2009
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23. Inhibition of tumour necrosis factor-alpha by antisense targeting produces immunophenotypical and morphological changes in injury-activated microglia and macrophages.

Author

Pearse DD, Pereira FC, Stolyarova A, Barakat DJ, and Bunge MB

Subjects
Animals, Female, Immunophenotyping methods, Macrophages drug effects, Microglia drug effects, Rats, Rats, Inbred F344, Spinal Cord Injuries pathology, Macrophages metabolism, Macrophages pathology, Microglia metabolism, Microglia pathology, Oligonucleotides, Antisense pharmacology, Spinal Cord Injuries metabolism, Tumor Necrosis Factor-alpha antagonists & inhibitors, Tumor Necrosis Factor-alpha genetics
Abstract

Microglia respond in a stereotypical pattern to a diverse array of pathological states. These changes are coupled to morphological and immunophenotypical alterations and the release of a variety of reactive species, trophic factors and cytokines that modify both microglia and their cellular environment. We examined whether a microglial-produced cytokine, tumour necrosis factor-alpha (TNF-alpha), was involved in the maintenance of microglial activation after spinal cord injury by selective inhibition using TNF-alpha antisense deoxyoligonucleotides (ASOs). Microglia and macrophages harvested from 3 d post-contused rat spinal cord were large and rounded (86.3 +/- 9.6%). They were GSA-IB4-positive (GSA-IB4(+)) (Griffonia simplicifolia lectin, microglia specific; 94.8 +/- 5.1%), strongly OX-42 positive (raised against a type 3 complement/integrin receptor, CD11b; 78.9 +/- 9.1%), ED-1 positive (a lysosomal marker shown to correlate well with immune cell activation; 97.2 +/- 2.6%) and IIA positive (antibody recognizes major histocompatibility complex II; 57.2 +/- 5.6%), indicative of fully activated cells, for up to 48 h after plating. These cells also secreted significant amounts of TNF-alpha (up to 436 pg/microg total protein, 16 h). Fluoroscein isothiocyanate-labelled TNF-alpha ASOs (5, 50 and 200 nm) added to the culture medium were taken up very efficiently into the cells (> 90% cells) and significantly reduced TNF-alpha production by up to 92% (26.5 pg/microg total protein, 16 h, 200 nm TNF-alpha ASOs). Furthermore, few of the treated cells at this time were round (5.4 +/- 2.7%), having become predominantly spindle shaped (74.9 +/- 6.3%) or stellate (21.4 +/- 2.7%); immunophenotypically, although all of them remained GSA-IB4 positive (91.6 +/- 6.2%), many were weakly OX-42 positive and few expressed either ED-1 (12.9 +/- 2.5%) or IIA (19.8 +/- 7.4%). Thus, the secretion of TNF-alpha early in spinal cord injury may be involved in autoactivating microglia/macrophages. However, at the peak of microglial activation after injury, the activation state of microglia/macrophages is not stable and this process may still be reversible by blocking TNF-alpha.

Published
2004
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