Platelets adhere to thrombin-treated endothelial cells in vitro.
Interaction of thrombin with vascular endothelial cells was investigated as a mechanism promoting platelet activation and adherence to endothelial monolayers. We found that pretreatment of endothelium with alpha-thrombin in the absence of platelets results in the attachment of platelets to endothelial cells after the removal of fluid-phase alpha-thrombin. This activity was eliminated by exposure of alpha-thrombin-pretreated endothelial cells to active site inhibitors of alpha-thrombin or by adding alpha-thrombin in the presence of excess diisopropyl fluorophosphate-inhibited thrombin, suggesting retention of active alpha-thrombin by a receptor-mediated mechanism. Morphological data and the results of [14C]serotonin release studies indicate that platelets are activated by alpha-thrombin-pretreated endothelium and that adherence represents aggregates of activated platelets as well as individual platelets. Adherence on alpha-thrombin-pretreated endothelium is dependent on divalent cations. Platelets also adhered to aortic segments pretreated with thrombin. The data of the current studies support the contention that alpha-thrombin can promote adherence of activated platelets to endothelial cells because of the binding and retention of alpha-thrombin to endothelial cells in a manner in which it remains active and available for platelet activation.
Department of Physiology, Albany Medical College of Union University 12208.
J E
JE
Kaplan
D G
DG
Moon
L K
LK
Weston
F L
FL
Minnear
P J
PJ
Del Vecchio
J M
JM
Shepard
J W
JW
Fenton
D000818:Animals; D001792:Blood Platelets / Q000502:physiology* / Q000648:ultrastructure; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000502:physiology*; D006629:Hirudins / Q000494:pharmacology; D008855:Microscopy, Electron, Scanning; D010973:Platelet Adhesiveness / Q000187:drug effects; D011651:Pulmonary Artery; D012701:Serotonin / Q000097:blood; D012756:Sheep; D013917:Thrombin / Q000502:physiology*
D006629:Hirudins; D012701:Serotonin; D013917:Thrombin