研究人员发现，凝血因子纤维蛋白是口腔粘膜屏障中性粒细胞功能的一个关键调节因子。研究人员证明，共生微生物群引发血管外纤维蛋白在口腔粘膜的沉积。纤维蛋白通过αMβ2整合素受体与中性粒细胞接触，并激活效应功能，包括活性氧的产生和中性粒细胞胞外陷阱的形成。在小鼠和人类中，这些免疫保护性的中性粒细胞功能在血浆蛋白介导的纤维蛋白溶酶受损的情况下会变成组织损伤。
一致的是，编码纤溶酶原的PLG遗传多态性与常见的牙周病形式有关。因此，纤维蛋白是中性粒细胞效应功能的一个重要调节因子，纤维蛋白-中性粒细胞的接触可能是一种普遍的粘膜疾病致病原因。
据悉，组织特异性线索对粘膜屏障的平衡至关重要。
附：英文原文
Title: Fibrin is a critical regulator of neutrophil effector function at the oral mucosal barrier
Author: 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, Niki M. Moutsopoulos
Issue&Volume: 2021-12-24
Abstract: Tissue-specific cues are critical for homeostasis at mucosal barriers. Here, we report that the clotting factor fibrin is a critical regulator of neutrophil function at the oral mucosal barrier. We demonstrate that commensal microbiota trigger extravascular fibrin deposition in the oral mucosa. Fibrin engages neutrophils through the αMβ2 integrin receptor and activates effector functions, including the production of reactive oxygen species and neutrophil extracellular trap formation. These immune-protective neutrophil functions become tissue damaging in the context of impaired plasmin-mediated fibrinolysis in mice and humans. Concordantly, genetic polymorphisms in PLG, encoding plasminogen, are associated with common forms of periodontal disease. Thus, fibrin is a critical regulator of neutrophil effector function, and fibrin-neutrophil engagement may be a pathogenic instigator for a prevalent mucosal disease.
DOI: abl5450
Source: https://www.science.org/doi/10.1126/science.abl5450