Schneider Andrea E, Sándor Noémi, Kárpáti Éva, Józsi Mihály
MTA-ELTE "Lendület" Complement Research Group, Department of Immunology, Eötvös Loránd University, 1117 Budapest, Hungary.
MTA-ELTE Immunology Research Group, Department of Immunology, Eötvös Loránd University, 1117 Budapest, Hungary.
Mol Immunol. 2016 Apr;72:37-48. doi: 10.1016/j.molimm.2016.02.011. Epub 2016 Mar 1.
Factor H (FH) is a major inhibitor of the alternative pathway of complement activation in plasma and on certain host surfaces. In addition to being a complement regulator, FH can bind to various cells via specific receptors, including binding to neutrophil granulocytes through complement receptor type 3 (CR3; CD11b/CD18), and modulate their function. The cellular roles of FH are, however, poorly understood. Because neutrophils are important innate immune cells in inflammatory processes and the host defense against pathogens, we aimed at studying the effects of FH on various neutrophil functions, including the generation of extracellular traps. FH co-localized with CD11b on the surface of neutrophils isolated from peripheral blood of healthy individuals, and cell-bound FH retained its cofactor activity and enhanced C3b degradation. Soluble FH supported neutrophil migration and immobilized FH induced cell spreading. In addition, immobilized but not soluble FH enhanced IL-8 release from neutrophils. FH alone did not trigger the cells to produce neutrophil extracellular traps (NETs), but NET formation induced by PMA and by fibronectin plus fungal β-glucan were inhibited by immobilized, but not by soluble, FH. Moreover, in parallel with NET formation, immobilized FH also inhibited the production of reactive oxygen species induced by PMA and by fibronectin plus β-glucan. Altogether, these data indicate that FH has multiple regulatory roles on neutrophil functions. While it can support the recruitment of neutrophils, FH may also exert anti-inflammatory effects and influence local inflammatory and antimicrobial reactions, and reduce tissue damage by modulating NET formation.
补体因子H（FH）是血浆中和某些宿主表面补体激活替代途径的主要抑制剂。除了作为补体调节剂外，FH还可通过特定受体与多种细胞结合，包括通过3型补体受体（CR3；CD11b/CD18）与中性粒细胞结合，并调节其功能。然而，FH的细胞作用尚不清楚。由于中性粒细胞是炎症过程和宿主抵御病原体的重要天然免疫细胞，我们旨在研究FH对各种中性粒细胞功能的影响，包括细胞外陷阱的产生。FH与从健康个体外周血分离的中性粒细胞表面的CD11b共定位，细胞结合的FH保留其辅因子活性并增强C3b降解。可溶性FH支持中性粒细胞迁移，固定化的FH诱导细胞铺展。此外，固定化而非可溶性的FH增强了中性粒细胞释放白细胞介素-8。单独的FH不会触发细胞产生中性粒细胞胞外陷阱（NETs），但由佛波酯（PMA）以及纤连蛋白加真菌β-葡聚糖诱导的NET形成受到固定化而非可溶性FH的抑制。此外，与NET形成同时，固定化的FH还抑制了由PMA以及纤连蛋白加β-葡聚糖诱导的活性氧的产生。总之，这些数据表明FH对中性粒细胞功能具有多种调节作用。虽然它可以支持中性粒细胞的募集，但FH也可能发挥抗炎作用并影响局部炎症和抗菌反应，并通过调节NET形成来减少组织损伤。
