title: Fibrin-incorporated vitronectin is involved in platelet adhesion and thrombus formation through homotypic interactions with platelet-associated vitronectin.
abstract: When a blood clot is formed, vitronectin (VN) is incorporated. Here we studied the consequence of VN incorporation for platelet interactions under flow. Perfusion of whole blood over a fibrin network, formed from purified fibrinogen, resulted in approximately 20% surface coverage with blood platelets. Incorporation of purified multimeric VN into the fibrin network resulted in a 2-fold increase in surface coverage with platelets and in enhancement of platelet aggregate formation. A human monoclonal antibody (huMab VN18), directed against the multimeric form of VN, inhibited platelet adhesion to the combined fibrin/VN matrix to the level of adhesion on fibrin alone. This inhibition was also shown when whole blood was perfused over a plasma-derived clot. Surprisingly, the inhibitory action of the antibody was not directed toward VN incorporated into the fibrin network but toward VN released from the platelets. We conclude that VN-potentiated platelet-clot interaction requires VN in the clot and multimeric VN bound to the platelet surface. Our results provide evidence that homotypic VN interactions contribute to platelet adhesion and aggregation to a blood clot. This report demonstrates for the first time that self-assembly of VN may provide a physiologically relevant contribution to platelet aggregation on a blood clot.
authors.affiliation: Department of Nephrology (C3P25), University Medical Centre, Albinusdreef 2, 2333 ZA Leiden, the Netherlands. h.c.deboer@lumc.nl
authors.forename: Ya-Ping
authors.initials: YP
authors.lastname: Wu
authors.forename: Haiko J
authors.initials: HJ
authors.lastname: Bloemendal
authors.forename: Emile E
authors.initials: EE
authors.lastname: Voest
authors.forename: Ton
authors.initials: T
authors.lastname: Logtenberg
authors.forename: Philip G
authors.initials: PG
authors.lastname: de Groot
authors.forename: Martijn F B G
authors.initials: MF
authors.lastname: Gebbink
authors.forename: Hetty C
authors.initials: HC
authors.lastname: de Boer
mesh_terms: D000911:Antibodies, Monoclonal / Q000187:drug effects; D001792:Blood Platelets / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D019281:Dimerization; D005337:Fibrin / Q000378:metabolism*; D006801:Humans; D010477:Perfusion; D010973:Platelet Adhesiveness / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D013927:Thrombosis / Q000209:etiology*; D019096:Vitronectin / Q000276:immunology / Q000378:metabolism* / Q000502:physiology*
chemical_list: D000911:Antibodies, Monoclonal; D019096:Vitronectin; D005337:Fibrin