HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Factor XIIIa supports microvascular endothelial cell adhesion and inhibits capillary tube formation in fibrin

Coagulation factor XIIIa is a transglutaminase that catalyzes covalent cross-link formation in fibrin clots. In this report, we demonstrate that factor XIIIa also mediates adhesion of endothelial cells and inhibits capillary tube formation in fibrin. The adhesive activity of factor XIIIa was not dependent on the transglutaminase activity, and did not involve the factor XIIIb-subunits. The adhesion was inhibited by 99% using a combination of monoclonal antibodies directed against integrin avb3 and b1-containing integrins, and was dependent on Mg21 or Mn21. Soluble factor XIIIa also bound to endothelial cells in solution, as detected by flow cytometry. In addition, factor XIIIa inhibited endothelial cell capillary tube formation in fibrin in a dose-dependent manner. Furthermore, the extent of inhibition differed in 2 types of fibrin. The addition of 10 to 100 mg/mL factor XIIIa produced a dose-dependent reduction in capillary tube formation of 60% to 100% in gA/gA fibrin, but only a 10% to 37% decrease in gA/g8 fibrin. These results show that factor XIIIa supports endothelial cell adhesion in an integrin-dependent manner and inhibits capillary tube formation. (Blood. 2000;95:2586-2592)