Conditions influencing the interaction of asialo von Willebrand factor with human platelets--the effects of external ionized calcium concentration and the role of arachidonate pathway.
We have studied the interaction of ASvWf with human platelets in PRP and in suspensions of washed platelets containing either physiological or low external ionized calcium concentration [Ca2+]o. In hirudin-PRP or in washed platelets in 1.5-2 mM CaCl2, ASvWf up to 50 micrograms/ml does not induce platelet aggregation or the release reaction. When [Ca2+]o is decreased by addition of citrate to hirudin-PRP or when no CaCl2 is added to washed platelet suspensions, ASvWf does induce platelet aggregation and the release reaction. In low [Ca2+]o, ASvWf interacts with platelet GPIb to cause primary aggregation of disc-shaped platelets to each other through GPIIb/IIIa, with or without added fibrinogen. This primary platelet aggregation leads to thromboxane A2 formation and secondary aggregation and the release reaction. With [Ca2+]o in the physiological range, there is less ASvWf interaction with GPIb, no primary platelet aggregation and no thromboxane A2 formation. The ASvWf-platelet interaction at physiological [Ca2+]o, however, enhances the platelet response to collagen or epinephrine.
Cattaneo
M
M
A. Bianchi Bonomi Hemophilia and Thrombosis Centre, University of Milano, Italy.
Mustard
J F
JF
Canciani
M T
MT
Richardson
M
M
Federici
A B
AB
Mannucci
P M
PM
D001095:Arachidonic Acids / Q000502:physiology*; D001212:Asialoglycoproteins; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D002118:Calcium / Q000032:analysis / Q000494:pharmacology*; D004357:Drug Synergism; D004492:Edetic Acid / Q000494:pharmacology; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011485:Protein Binding; D013929:Thromboxane B2 / Q000096:biosynthesis; D014841:von Willebrand Factor / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000302:isolation & purification / Q000378:metabolism
D001095:Arachidonic Acids; D001212:Asialoglycoproteins; D010975:Platelet Aggregation Inhibitors; C044131:asialo-von Willebrand Factor; D014841:von Willebrand Factor; D013929:Thromboxane B2; D006493:Heparin; D004492:Edetic Acid; D002118:Calcium