Fibrin-mediated vascular injury: demonstration of vascular endothelial cell retraction in response to soluble fibrin-associated factors.
Until recently, fibrin deposition has been generally viewed as a ubiquitous, but passive, characteristic of both acute and chronic inflammatory processes. An increasing number of studies, however, suggest that fibrin deposition and fibrin degradation products may play an active role in these reactions, especially in the development of tissue edema. As the intravascular-to-extravascular "gateway" for movement of fluids, solutes, and cells must pass, the vascular endothelial cells may play a crucial regulatory role in this process. Recent evidence suggests that the interaction of whole fibrin with endothelial cells may lead to endothelial cell injury. This work examines the role of fibrin and fibrinogen-associated factors (FAF) in the injury of cultured vascular endothelial cells (VEC). It was demonstrated that endothelial cell injury, evidenced by retraction of the cells, was induced not only by whole fibrin, but also by soluble thrombin-cleaved products of fibrinogen. This reaction was shown to be specific for endothelial cells, nontoxic, and completely reversible. The general biological importance of this reaction was further underscored in that active factors could be generated from fibrinogen obtained from a number of species. Reproducible, quantitative assays of cultured endothelial cell retraction were developed to aid in the characterization of the endothelial cell-specific FAFs.
D000818:Animals; D001769:Blood; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003470:Culture Media; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology*; D005337:Fibrin / Q000494:pharmacology / Q000502:physiology*; D005338:Fibrin Fibrinogen Degradation Products / Q000494:pharmacology; D005340:Fibrinogen / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D011651:Pulmonary Artery; D013917:Thrombin / Q000494:pharmacology; D014652:Vascular Diseases / Q000209:etiology / Q000473:pathology*
D003470:Culture Media; D005338:Fibrin Fibrinogen Degradation Products; D010455:Peptides; D005337:Fibrin; D005340:Fibrinogen; D013917:Thrombin