Covalent crosslinking of von Willebrand factor to fibrin.
Factor XIIIa crosslinks a limited number of substrates via epsilon(gamma-glutamyl)-lysyl bond formation. It crosslinks fibrin to itself, alpha 2-plasmin inhibitor and fibronectin to fibrin, and fibronectin to collagen. Results presented here show that plasma von Willebrand factor (vWF) is a substrate for factor XIIIa and can be crosslinked to fibrin during gel formation. vWF-fibrin crosslinking was studied in purified systems and in plasma with 125I-vWF and 131I-fibrinogen. vWF incorporation into fibrin increased with time or increasing factor XIIIa. After electrophoresis of dissolved clots, distribution of 125I and 131I was measured and showed that vWF was crosslinked to the alpha chain of fibrin and entered the high-mol-wt alpha polymer. vWF-fibrin crosslinking decreased the initial rate of alpha polymer formation. Crosslinking of vWF polymer to itself could not be demonstrated under physiologic conditions but occurred if vWF was reduced first. Factor XIIIa catalyzed incorporation of putrescine into both monomeric and polymeric vWF. Altogether, these studies indicate that factor XIIIa can readily form covalent bonds between glutamine in vWF and lysine in fibrin alpha chains. This reaction occurs readily in vitro when plasma clotting is slow and may occur in vivo under similar conditions.
Hada
M
M
Kaminski
M
M
Bockenstedt
P
P
McDonagh
J
J
D001780:Blood Coagulation Tests; D003432:Cross-Linking Reagents; D005176:Factor XIII / Q000032:analysis*; D005337:Fibrin / Q000032:analysis*; D005340:Fibrinogen / Q000032:analysis; D005782:Gels; D005973:Glutamine / Q000032:analysis; D006801:Humans; D066298:In Vitro Techniques; D008239:Lysine / Q000032:analysis; D011700:Putrescine / Q000032:analysis; D011503:Transglutaminases; D014841:von Willebrand Factor / Q000032:analysis*
D003432:Cross-Linking Reagents; D005782:Gels; D014841:von Willebrand Factor; D005973:Glutamine; D005337:Fibrin; D005340:Fibrinogen; D005176:Factor XIII; D011503:Transglutaminases; D008239:Lysine; D011700:Putrescine