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6. Fluorescence Lifetime to image epidermal ionic concentrations

Author

Behne, MJ, Barry, NP, Moll, I, Gratton, E, and Mauro, TM

Subjects
epidermis, fluorescence lifetime imaging, pH, calcium
Abstract

Measurements of ionic concentrations in skin have traditionally been performed with an array of methods which either did not reveal detailed localization information, or only provided qualitative, not quantitative information. FLIM combines a number of advantages into a method ideally suited to visualize concentrations of ions such as FT in intact, unperturbed epidermis and stratum corneum (SC). Fluorescence lifetime is dye concentration- independent, the method requires only low light intensities and is therefore not prone to photobleaching or phototoxic artifacts, and because multiphoton lasers of IR wavelength are used, light penetrates deep into intact tissue. The standard method to measure SC pH is the flat pH electrode, which provides reliable information only about surface pH changes, without further vertical or subcellular spatial resolution; i.e., specific microdomains such as the corneocyte interstices are not resolved, and the deeper SC is inaccessible without resorting to inherently disruptive stripping methods. Furthermore, the concept of a gradient of pH through the SC stems from such stripping experiments, but other confirmation for this concept is lacking. Our investigations into the SC pH distribution so far have revealed the crucial role of the Sodium/Hydrogen Antiporter NHE1 in generation of SC acidity, the colocalization of enzymatic lipid processing activity in the SC with acidic domains of the SC, and the timing and localization of emerging acidity in the SC of newborns. Together, these results have led to an improved understanding of the SC pH, its distribution, origin, and regulation. Future uses for this method include measurements of other ions important for epidermal processes, such as Ca2+, and a quantitative approach to topical drug penetration.

Published
2004

14. Merkel-Zellkarzinom

Author

Moll, I., Kerl, Helmut, editor, Garbe, Claus, editor, Cerroni, Lorenzo, editor, and Wolff, Helmut H., editor

Published
2003
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16. Endothelial RBPJ is essential for the education of tumor-associated macrophages

Author

Alsina-Sanchis E, Mülfarth R, Moll I, Böhn S, Wiedmann L, Jordana-Urriza L, Ziegelbauer T, Zimmer E, Taylor J, De Angelis Rigotti F, Stögbauer A, Giaimo BD, Cerwenka A, Borggrefe T, Fischer A, and Rodriguez-Vita J

Abstract

Epithelial ovarian cancer (EOC) is one of the most lethal gynecological cancers worldwide. EOC cells educate tumor-associated macrophages (TAM) through CD44-mediated cholesterol depletion to generate an immunosuppressive tumor microenvironment (TME). In addition, tumor cells frequently activate Notch1 receptors on endothelial cells (EC) to facilitate metastasis. However, further work is required to establish whether the endothelium also influences the education of recruited monocytes. Here, we report that canonical Notch signaling through RBPJ in ECs is an important player in the education of TAMs and EOC progression. Deletion of Rbpj in the endothelium of adult mice reduced infiltration of monocyte-derived macrophages into the TME of EOC and prevented the acquisition of a typical TAM gene signature; this was associated with stronger cytotoxic activity of T cells and decreased tumor burden. Mechanistically, CXCL2 was identified as a novel Notch/RBPJ target gene that regulated the expression of CD44 on monocytes and subsequent cholesterol depletion of TAMs. Bioinformatic analysis of ovarian cancer patient data showed that increased CXCL2 expression is accompanied by higher expression of CD44 and TAM education. Together, these findings indicate that EOC cells induce the tumor endothelium to secrete CXCL2 in order to establish an immunosuppressive microenvironment.

Published
2022

23. Phlebologie an deutschen Hautkliniken: Eine Bestandsaufnahme im Auftrag der Deutschen Gesellschaft für Phlebologie

Author

Reich-Schupke, S., Alm, J., Altmeyer, P., Bachter, D., Bayerl, C., Beissert, S., Bieber, T., Böhmer, J., Dill, D., Dippel, E., Dücker, P., Effendy, I., El Gammal, S., Elsner, P., Enk, A., Feldmann-Böddeker, I., Frank, H., Gehring, W., Gieler, U., Goebeler, M., Görge, T., Gollnick, H., Grabbe, S., Gross, G., Gudat, W., Happ, A., Herbst, R., Hermes, B., Hoff, N.-P., John, S.M., Jungelhülsing, M., Jünger, M., Kaatz, M., Kapp, A., Kaufmann, R., Klode, J., Knaber, K., König, A., Krieg, T., Kohl, P., Kowalzick, L., Lehmann, P., Löffler, H., Maschke, J., Marsch, W., Mechtel, D., Mohr, P., Moll, I., Müller, M., Nashan, D., Ockenfels, H.M., Peter, R.U., Pillekamp, H., Rompel, R., Ruzicka, T., Salfeld, K., Sander, C., Schaller, J., Scharffetter-Kochanek, K., Schuler, G., Schulze, H.-J., Schwarz, T., Splieth, B., Stege, H., Stolz, W., Strölin, A., Tran, H., Tronnier, M., Ulrich, J., Vogt, T., Wagner, G., Welzel, J., Willgeroth, T., Wollina, U., Zillikens, D., Zouboulis, C.C., Zuberbier, T., Zutt, M., and Stücker, M.

Published
2013
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25. 205P Immunomodulation in early triple-negative breast cancer (TNBC): Analysis of soluble markers as predictive biomarkers to neoadjuvant chemotherapy in TNBC

Author

Nunez Abad, M., primary, Torres Martínez, S., additional, Ferriol Martinez, C., additional, Escorihuela, E., additional, Garcia Gonzalez, C., additional, Franco de la Rosa, M.M., additional, Montagud Inza, L., additional, García García, J.Á., additional, Gumbau Puchol, V., additional, Castañer Puga, C., additional, Matoses Ortiz, P., additional, Barreres Moll, I., additional, Godes Sanz de Bremond, M.J., additional, Calabuig-Fariñas, S., additional, Caballero Díaz, C., additional, Blasco Cordellat, A., additional, Camps, C.J., additional, and Iranzo, V., additional

Published
2021
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