Fibrin-mediated vascular injury. Identification of fibrin peptides that mediate endothelial cell retraction.
The deposition of fibrin, a ubiquitous component of acute and chronic inflammatory reactions, has been implicated by a number of recent studies as playing an active role in inflammation. In particular, fibrin deposition has been implicated in the development of tissue edema. As the "gateway" through which intravascular-to-extravascular movement of fluid, nutrients, and cells must pass, the vascular endothelial cells play a crucial regulatory role in this process. In support of this concept, recent studies in this laboratory have demonstrated that endothelial cells retract not only in the presence of fibrin but also in the presence of low molecular weight cleavage products of fibrinogen. It was further shown that this reaction was 1) specific for both vascular and corneal endothelial cells, 2) nontoxic, and 3) completely reversible. The present work examined the physiochemical nature of these endothelial-cell reactive factors. It was demonstrated by the use of enzymatically derived and synthetic fibrinogen peptides, that the active soluble fibrinogen-derived factor was associated with the amino-terminal end of the B chain of fibrinogen. The active factor has been tentatively identified as the B beta peptides, which is a primary plasmin cleavage product of fibrinogen and contains the thrombin-generated fibrinopeptide B. It is thus suggested that soluble, endothelial-cell-reactive peptides are released during both fibrinogenesis and fibrinolysis and, as such, modulate endothelial cell functions in vivo.
D000818:Animals; D000906:Antibodies / Q000502:physiology; D001667:Binding, Competitive; D002199:Capillary Permeability; D002417:Cattle; D002725:Chloroform; D002851:Chromatography, High Pressure Liquid; D002852:Chromatography, Ion Exchange; D004727:Endothelium / Q000166:cytology* / Q000502:physiology; D005337:Fibrin / Q000502:physiology*; D005338:Fibrin Fibrinogen Degradation Products / Q000502:physiology*; D005340:Fibrinogen / Q000276:immunology; D006168:Guinea Pigs; D006358:Hot Temperature; D006801:Humans; D008970:Molecular Weight; D010446:Peptide Fragments; D011651:Pulmonary Artery / Q000503:physiopathology; D011817:Rabbits
D000906:Antibodies; D005338:Fibrin Fibrinogen Degradation Products; D010446:Peptide Fragments; C035285:fibrinogen Bbeta (1-42); D002725:Chloroform; D005337:Fibrin; D005340:Fibrinogen