Endothelial cell responses to fibrin mediated by FPB cleavage and the amino terminus of the beta chain.
Endothelial cells (EC) interact with fibrin at sites of vascular injury, thrombosis, inflammation and tumor growth, whereas they are quiescent 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 with thrombin, which cleaves both fibrinopeptide A (FPA) and fibrinopeptide B (FPB), with Reptilase, which cleaves only FPA, and with contortrix procoagulant to cleave only FPB. Fibrin with FPB cleavage stimulated release of von Willebrand factor from EC Weibel-Palade bodies and also supported cell spreading. Involvement of the amino terminus of the fibrin beta chain in the response was shown by stimulation of von Willebrand 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 pattern of fibrinopeptide cleavage or by the removal of peptide beta 15-42 from fibrin. The results indicate that separate sites on the fibrin molecule mediate adhesion and spreading, and that the latter requires cleavage of FPB and the new amino terminus of the beta chain. They further suggest that cellular responses to fibrin are regulated by the proteolytic cleavages and conformational changes that convert fibrinogen to fibrin and may also be modulated by plasmic or elastase degradation.
Francis
C W
CW
Department of Medicine, University of Rochester School of Medicine & Dentistry, New York.
Bunce
L A
LA
Sporn
L A
LA
D000595:Amino Acid Sequence; D000818:Animals; D002448:Cell Adhesion; D004730:Endothelium, Vascular / Q000502:physiology*; D005337:Fibrin / Q000502:physiology*; D005340:Fibrinogen / Q000737:chemistry / Q000378:metabolism*; D005344:Fibrinopeptide A / Q000378:metabolism; D005345:Fibrinopeptide B / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000473:pathology; D010973:Platelet Adhesiveness; D013927:Thrombosis / Q000503:physiopathology; D014841:von Willebrand Factor / Q000378:metabolism
D046911:Macromolecular Substances; D014841:von Willebrand Factor; D005344:Fibrinopeptide A; D005345:Fibrinopeptide B; D005337:Fibrin; D005340:Fibrinogen