Molecular mechanism of the interaction of subendothelial microfibrils with blood platelets.
This short review summarizes the present state of our knowledge concerning the mechanisms of the interaction between subendothelial microfibrils and blood platelets. Microfibrils associated with elastin and with basement membranes have been shown to be able to promote platelet adhesion and subsequent activation and aggregation. A 128 kDa thrombospondin (TSP)-like glycoprotein of microfibrils (GP 128) is involved in their reactivity towards platelets, as established from specific inhibition by antibodies against GP 128 and against TSP of the microfibril-platelet interaction. This interaction only occurs in the presence of plasma von Willebrand factor (vWF). VWF effectively binds to microfibrils; this binding does not implicate GP 128, but a 97 kDa protein of microfibrils not yet characterized. In addition, from data based on inhibition of platelet adhesion and aggregation by monoclonal antibodies against platelet membrane glycoprotein Ib (GP Ib), it appears that GP Ib, a platelet membrane receptor for vWF, acts in the vWF dependent microfibril-platelet interaction as a receptor for VWF bound to protein 97 kDa in microfibrils. A tentative model is presented to illustrate the complex mechanism of the microfibril-platelet interactions: recognition of vWF bound to microfibrils by GP Ib would be the first step, which would then allow subsequent binding of GP 128 to its receptor on the platelet membrane.
Legrand
Y J
YJ
INSERM U353, Institut d'Hématologie, Hôpital Saint-Louis, Paris, France.
Fauvel-Lafève
F
F
D008841:Actin Cytoskeleton / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001158:Arteries / Q000378:metabolism*; D001485:Basement Membrane / Q000378:metabolism; D001792:Blood Platelets / Q000378:metabolism*; D002417:Cattle; D003429:Cross Reactions; D004549:Elastin / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D010973:Platelet Adhesiveness; D010980:Platelet Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D019699:Thrombospondins; D014841:von Willebrand Factor / Q000378:metabolism
D000911:Antibodies, Monoclonal; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D019699:Thrombospondins; D014841:von Willebrand Factor; C028254:von Willebrand factor receptor; D004549:Elastin