Neutrophil α-defensins promote thrombosis in vivo by altering fibrin formation, structure, and stability.

ABSTRACT: Inflammation and thrombosis are integrated, mutually reinforcing processes, but the interregulatory mechanisms are incompletely defined. Here, we examined the contribution of α-defensins (α-defs), antimicrobial proteins released from activated human neutrophils, on clot formation in vitro and in vivo. Activation of the intrinsic pathway of coagulation stimulates release of α-defs from neutrophils. α-Defs accelerate fibrin polymerization, increase fiber density and branching, incorporate into nascent fibrin clots, and impede fibrinolysis in vitro. Transgenic mice (Def⁺⁺) expressing human α-Def-1 developed larger, occlusive, neutrophil-rich clots after partial inferior vena cava (IVC) ligation than those that formed in wild-type (WT) mice. IVC thrombi extracted from Def⁺⁺

SUBMITTER: Abu-Fanne R 

PROVIDER: S-EPMC6356988 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature