A 130-kDa protein on endothelial cells binds to amino acids 15-42 of the B beta chain of fibrinogen.

Factors which stimulate the release of von Willebrand factor (vWf) from endothelial cell Weibel-Palade bodies and which induce the expression of the leukocyte-binding adhesion molecule P-selectin (PADGEM, GMP-140, CD62) on the endothelial cell surface remain incompletely characterized. Fibrin but not fibrinogen is a potent stimulus for the release of stored von Willebrand factor from endothelial cells. Removal of fibrinopeptides A and B from fibrinogen occurs during the formation of fibrin, and the removal of fibrinopeptide B is a requirement for fibrin to induce vWf secretion. The cleavage of fibrinopeptide A by reptilase enzyme forms a fibrin gel yet it is incapable of stimulating Weibel-Palade body degranulation. As a consequence of removing fibrinopeptide B, B beta 15-42 becomes the new NH2 terminus of the beta chain of fibrin. We have shown that the peptide B beta 15-42 in solution inhibits the release of vWf stimulated by fibrin. In addition, B beta 15-42 coupled to ovalbumin supports the binding and spreading of endothelial cells, while a scrambled form of this peptide coupled to the same carrier does not. We investigated whether these determinants near the amino terminus of the beta chain of fibrin bind to a specific protein on the surface of endothelial cells. A 130-kDa protein was isolated from surface-labeled human umbilical vein endothelial cells by specific binding to B beta 15-42 immobilized on Sepharose. This glycoprotein was eluted with the B beta 15-42 peptide in solution but not with the scrambled form of this peptide. The fibrin-derived peptides B beta 19-26 and B beta 37-56-cysteine were also incapable of eluting the 130-kDa protein bound to immobilized B beta 15-42 as were the arginine-glycine-aspartic acid-serine RGDS tetrapeptide and EDTA. The 130-kDa protein is recognized neither by antibodies to the known integrins found on endothelial cells nor by antibodies to CD31 (endoCAM, PECAM-1), a member of the immunoglobulin family of receptors found on endothelial cells. The beta chain of fibrin thus contains a sequence near its amino terminus which specifically binds to what is likely a novel endothelial cell surface protein. This glycoprotein may promote endothelial cell adhesion to fibrin during the wound healing process and is a candidate for a receptor involved in fibrin-mediated release of Weibel-Palade bodies from endothelial cells.