title: Impaired platelet adhesion to lysed fibrin, whereas neutrophil adhesion remains intact under conditions of flow.
abstract: Vessel wall injury induces the formation of a haemostatic plug. Restoration of vascular integrity should involve cessation of further platelet and fibrin deposition and subsequent removal of these thrombi by both the fibrinolytic system and proteases delivered by infiltrating inflammatory cells. We hypothesized that adhesion of platelets and inflammatory cells [polymorphonuclear leucocyte (PMN)] to fibrin is differently supported after exposure of fibrin during fibrinolysis. Fibrin surfaces were exposed to fibrinolytic agents, and platelet and PMN adhesion was studied under conditions of flow. Specific adhesion of platelets to preformed fibrin was reduced by fibrinolytic treatment of the fibrin. PMN adhesion to fibrin was only slightly affected even after 180 min exposure to plasmin. With fibrin still present after fibrinolytic treatment, the impaired platelet adhesion seems explained by loss of the primary platelet adhesion site gamma400-411 on fibrin. PMN binding to fibrin clearly depends on other sites that are less degraded by fibrinolysis. We have shown that PMN adhesion in flowing blood to lysed fibrin was still present, whereas platelet adhesion was impaired due to the loss of the primary platelet adhesion site gamma400-411. Based on our in-vitro perfusion model, we conclude that fibrinolysis specifically interferes with the thrombogenicity of fibrin in the haemostatic plug, whereas the inflammatory response is preserved. The latter may participate in the long-term removal and restructuration of the plug.
authors.affiliation: Thrombosis and Haemostasis Laboratory, Department of Haematology, University Medical Center Utrecht, The Netherlands. jaremijn@hotmail.com
authors.forename: Jasper A
authors.initials: JA
authors.lastname: Remijn
authors.forename: Paula
authors.initials: P
authors.lastname: Da Costa Martins
authors.forename: Martin J W
authors.initials: MJ
authors.lastname: Ijsseldijk
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Sixma
authors.forename: Philip G
authors.initials: PG
authors.lastname: de Groot
authors.forename: Jaap J
authors.initials: JJ
authors.lastname: Zwaginga
mesh_terms: D000941:Antigens / Q000502:physiology; D002448:Cell Adhesion / Q000502:physiology; D005337:Fibrin / Q000276:immunology; D005342:Fibrinolysis / Q000502:physiology*; D006801:Humans; D009504:Neutrophils / Q000166:cytology*; D010973:Platelet Adhesiveness; D012039:Regional Blood Flow
chemical_list: D000941:Antigens; D005337:Fibrin