Interaction of asialo @entity2880 factor with glycoprotein Ib induces fibrinogen binding to the XXXX .

@entity1423 @entity8325 @entity2881 @entity1427 @entity1317 @entity857 @entity2880
@entity2880 factor ( @entity2881 ) is necessary for the initial attachment of platelets to exposed subendothelium, particularly under flow conditions like those prevailing in the microcirculation. Little is known about its possible participation in subsequent events leading to formation of platelet thrombi at sites of @entity1317 . We addressed this question by studying the mechanisms by which desialylated @entity2881 induces @entity1423 in the absence of any other stimulus. Asialo @entity2881 , unlike the native molecule, does not require @entity8325 to interact with platelets. Agglutination induced by @entity8325 is largely independent of active platelet metabolism and only partially reflects physiological events. We have shown here that binding of asialo @entity2881 to platelets was accompanied by release of dense granule content and subsequent @entity857 -dependent fibrinogen binding to receptors on the glycoprotein (GP) IIb/IIIa complex. The initial interaction of asialo @entity2881 with platelets was mediated by GPIb, as shown by blocking obtained with monoclonal antibody. Inhibition of this initial interaction completely abolished @entity1423 induced by asialo @entity2881 . The same effect was obtained with a monoclonal anti- @entity1427 /IIIa antibody. This, however, did not block asialo @entity2881 binding to platelets, but rather inhibited subsequent fibrinogen binding induced by asialo @entity2881 . Therefore, the latter process was also essential for @entity1423 under the conditions described. At saturation, asialo @entity2881 induced binding of between 3.2 and 27.7 X 10(3) fibrinogen molecules/platelet, with an apparent dissociation constant between 0.28 and 1.18 X 10(-6) M. This study shows that asialo, and possibly native, @entity2881 acts as a platelet agonist after its binding to GPIb and induces aggregation through a pathway dependent on @entity1427 /IIIa-related receptors.
