title: The interaction between factor H and VWF increases factor H cofactor activity and regulates VWF prothrombotic status.
abstract: Vascular endothelial cells (ECs) link hemostasis, thrombosis, and complement. ECs synthesize both the clotting initiator von Willebrand factor (VWF) and the complement regulator factor H (FH). VWF is stored in EC Weibel-Palade bodies (WPBs), but the intracellular location of FH is not well defined. We found that FH colocalizes with VWF in WPBs of human umbilical vein ECs. Moreover, FH bound to VWF with an apparent nanomolar affinity and the complex was present in normal plasma. The binding of VWF to FH enhanced FH cofactor activity toward factor I-mediated downregulation of complement activation. Besides, this interaction inhibited ADAMTS13-mediated proteolysis of VWF and promoted platelet aggregation. Here, we describe a novel interaction between complement and hemostasis. The simultaneous secretion of VWF and FH by activated ECs may promote adhesion of platelets to endothelial injury sites to assure wound healing, simultaneously dampening the proinflammatory effect of complement to limit bystander tissue damage.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale.
authors.forename: Julie
authors.initials: J
authors.lastname: Rayes
authors.forename: Lubka T
authors.initials: LT
authors.lastname: Roumenina
authors.forename: Jordan D
authors.initials: JD
authors.lastname: Dimitrov
authors.forename: Yohann
authors.initials: Y
authors.lastname: Repessé
authors.forename: Mathieu
authors.initials: M
authors.lastname: Ing
authors.forename: Olivier
authors.initials: O
authors.lastname: Christophe
authors.forename: T Sakari
authors.initials: TS
authors.lastname: Jokiranta
authors.forename: Lise
authors.initials: L
authors.lastname: Halbwachs-Mecarelli
authors.forename: Annie
authors.initials: A
authors.lastname: Borel-Derlon
authors.forename: Srinivas V
authors.initials: SV
authors.lastname: Kaveri
authors.forename: Véronique
authors.initials: V
authors.lastname: Frémeaux-Bacchi
authors.forename: Sébastien
authors.initials: S
authors.lastname: Lacroix-Desmazes
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism; D000071120:ADAMTS13 Protein; D003167:Complement Activation; D017242:Complement Factor H / Q000737:chemistry* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology; D004797:Enzyme-Linked Immunosorbent Assay; D006487:Hemostasis; D006579:Heterozygote; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology; D006801:Humans; D047468:Immunoprecipitation; D007249:Inflammation; D011485:Protein Binding; D025941:Protein Interaction Mapping; D020349:Surface Plasmon Resonance; D013927:Thrombosis; D020302:Weibel-Palade Bodies / Q000378:metabolism; D014841:von Willebrand Factor / Q000737:chemistry* / Q000378:metabolism
chemical_list: D014841:von Willebrand Factor; D017242:Complement Factor H; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human