1. Fibrin is a critical regulator of neutrophil effector function at the oral mucosal barrier
- Author
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Lakmali M. Silva, Andrew D. Doyle, Teresa Greenwell-Wild, Nicolas Dutzan, Collin L. Tran, Loreto Abusleme, Lih Jiin Juang, Jerry Leung, Elizabeth M. Chun, Andrew G. Lum, Cary S. Agler, Carlos E. Zuazo, Megan Sibree, Priyam Jani, Vardit Kram, Daniel Martin, Kevin Moss, Michail S. Lionakis, Francis J. Castellino, Christian J. Kastrup, Matthew J. Flick, Kimon Divaris, Thomas H. Bugge, and Niki M. Moutsopoulos
- Subjects
Male ,Fibrin ,Multidisciplinary ,Neutrophils ,Fibrinolysis ,Alveolar Bone Loss ,Gingiva ,Mouth Mucosa ,Fibrinogen ,Macrophage-1 Antigen ,Plasminogen ,Extracellular Traps ,Polymorphism, Single Nucleotide ,Neutrophil Activation ,Gastrointestinal Microbiome ,Mice ,Animals ,Humans ,Female ,Fibrinolysin ,RNA-Seq ,Periodontitis ,Reactive Oxygen Species ,Immunity, Mucosal - Abstract
Fibrin gums up the works Plasmin is an abundant plasma protease that cleaves and deactivates the clot-associated protein fibrin. Human deficiencies in plasmin and its inactive proenzyme form, plasminogen (PLG), cause severe inflammation in mucosal tissues such as the mouth and eyes. Silva et al . report that, like humans, mice lacking plasminogen accumulate extravascular fibrin and develop an oral pathology that phenocopies human ligneous periodontitis (see the Perspective by Vicanolo and Hidalgo). The excess fibrin activates neutrophils through the αMβ2 (Mac-1) integrin receptor, which triggers the production of reactive oxygen species and neutrophil extracellular traps. Additionally, certain human polymorphisms in the PLG gene were found to be associated with increased likelihood of developing periodontitis, suggesting that fibrin–neutrophil interactions may be an attractive target for future treatments of this prevalent disease. —STS
- Published
- 2021
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