fibrinopeptide-b and Inflammation

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.

Topics: Amino Acid Sequence; Animals; Cell Adhesion; Endothelium, Vascular; Fibrin; Fibrinogen; Fibrinopeptide A; Fibrinopeptide B; Humans; Inflammation; Macromolecular Substances; Molecular Sequence Data; Neoplasms; Platelet Adhesiveness; Thrombosis; von Willebrand Factor

Topics: Blood Coagulation; Bradykinin; Fibrinopeptide A; Fibrinopeptide B; Humans; Inflammation; Thrombophlebitis

Carrageenin-induced inflammatory rat paw swelling was significantly inhibited by intraperitoneal injection of rat fibrinogen. Whole-body radioscanning of the rat after intraperitoneal administration of 131I-labeled fibrinogen revealed the accumulation of radiolabeled material in the inflammed rat paw. Resorption studies showed that not more than 4% of the intraperitoneally administered [125I] fibrinogen could be demonstrated in the peripheral blood. Furthermore only 1/3 of this circulating radiolabeled protein was able to take part in clot formation, suggesting that inhibition of edema formation is mediated by fibrinogen-derived split products. This is further supported by the finding that rat fibrinopeptides, released by the action of thrombin, also diminish edema formation both after intracardial and intraperitoneal injection into carrageenin-stimulated rats.

Topics: Animals; Carrageenan; Dose-Response Relationship, Drug; Edema; Fibrinogen; Fibrinopeptide A; Fibrinopeptide B; Inflammation; Male; Rats; Rats, Inbred Strains