THE ROLE OF PUTATIVE FIBRINOGEN A-ALPHA-CHAIN, B-BETA-CHAIN, AND GAMMA-A-CHAIN INTEGRIN BINDING-SITES IN ENDOTHELIAL CELL-MEDIATED CLOT RETRACTION

In this study, endothelial cell-mediated clot retraction was supported by fibrin generated from several purified fractions of plasma fibrino gen, purified proteolytic fragments of plasma fibrinogen, recombinant normal fibrinogen, and recombinant variant fibrinogen, These results w ere surprising because some of these fibrinogens lack domains that are known binding sites for the integrin receptors that support clot retr action. Specifically, fibrinogens lacking A alpha-chain RGD residues a t 572-574 or lacking the gamma-chain residues AGDV 408-411 supported e ndothelial cell-mediated clot retraction as well as intact fibrinogen, Thus, clot retraction mediated by endothelial cells is not dependent on either of these sites, A variety of monoclonal antibodies against t he integrin alpha(v) beta(3) partially inhibited the endothelial cell- mediated retraction of clots formed from plasma fibrinogen, As expecte d, an antibody to the platelet integrin alpha(IIb)beta(3) did not inhi bit endothelial cell-mediated clot retraction. These results indicate that this retraction is mediated at least in part by alpha(v) beta(3). These results support the conclusion that (a) neither of the two fibr inogen cell binding sites described above is required to support clot retraction or that (b) either site alone or in conjunction with other fibrin(ogen) region(s) can support clot retraction, Thus, endothelial cell-mediated clot retraction appears to be dependent on fibrinogen ce ll binding sites other than those required to support adhesion of rest ing platelets to immobilized fibrinogen and platelet aggregation.