ENDOTHELIAL-CELL RESPONSES TO FIBRIN MEDIATED BY FPB CLEAVAGE AND THEAMINO-TERMINUS OF THE BETA-CHAIN

Endothelial cells (EC) interact with fibrin at sites of vascular injur y, thrombosis, inflammation and tumor growth, whereas they are quiesce nt when exposed to circulating fibrinogen. To determine the structural basis for specific interaction with fibrin we have characterized the response of EC to fibrin of varying structure. Fibrin was prepared wit h thrombin, which cleaves both fibrinopeptide A (FPA) and fibrinopepti de B (FPB), with Reptilase, which cleaves only FPA, and with contortri x procoagulant to cleave only FPB. Fibrin with FPB cleavage stimulated release of von Willebrand factor from EC Weibel-Palade bodies and als o supported cell spreading. Involvement of the amino terminus of the f ibrin beta chain in the response was shown by stimulation of von Wille brand factor release by the peptide beta 15-42. Also, fibrin prepared from a fibrinogen derivative lacking residues 15-42 of the beta chain failed to support EC spreading. EC adhesion was unaffected by the patt ern of fibrinopeptide cleavage or by the removal of peptide beta 15-42 from fibrin. The results indicate that separate sites on the fibrin m olecule mediate adhesion and spreading, and that the latter requires c leavage of FPB and the new amino terminus of the beta chain. They furt her suggest that cellular responses to fibrin are regulated by the pro teolytic cleavages and conformational changes that convert fibrinogen to fibrin and may also be modulated by plasmic or elastase degradation .