Human neutrophil alpha-defensins induce formation of fibrinogen and thrombospondin-1 amyloid-like structures and activate platelets via glycoprotein IIb/IIIa.

摘要: Summary.  Background:  Human neutrophil α-defensins (HNPs) are important constituents of the innate immune system. Beyond their antimicrobial properties, HNPs also have pro-inflammatory features. While in plasma from healthy individuals barely detectable, level is strongly elevated septic and patients with acute coronary syndromes. Objectives:  As thrombosis inflammation intertwined processes activation human polymorphonuclear leukocytes (PMNL) subsequent degranulation associated full surrounding platelets, we studied effect on platelet function. Methods:  The parameters apoptosis was investigated via aggregometry, flow cytometry, confocal microscopy ELISA technique. Results:  It found that activate platelets pathophysiologically relevant doses, inducing fibrinogen thrombospondin-1 binding, aggregation, granule secretion, sCD40L shedding, procoagulant activity. bound directly to membrane, induced membrane pore formation, microparticle mitochondrial depolarization caspase-3-activity. Confocal revealed HNP-induced formation polymeric amyloid-like structures, which microorganisms. Platelets adhered these structures formed aggregates. Blocking glycoprotein IIb/IIIa (GPIIb/IIIa) markedly inhibited activation. In addition, heparin, heparinoid, serpins α2-macroglobulin, all bind HNPs, blocked HNP-1-induced contrast direct thrombin inhibitors such as hirudin. Conclusions:  induce by proteins. entrapped bacteria fungi, they might reflect an additional function host defense. described mechanism links again infection.