INTERACTION OF INTEGRIN ALPHA(IIB)BETA(3) WITH MULTIPLE FIBRINOGEN DOMAINS DURING PLATELET-ADHESION

We have investigated how modulation of integrin alpha(IIb)beta(3) func tion influences the mechanisms that initiate platelet thrombus formati on onto surface-bound fibrinogen and isolated fibrinogen domains, Unde r stationary conditions and with full activation of platelets blocked by prostaglandin E(1), the carboxyl-terminal gamma(400-411) sequence i s necessary for establishing initial contact with the immobilized subs trate. Molecules containing a single copy of this sequence, like the p lasmin-generated fibrinogen fragment D, support platelet spreading, bu t the resulting attachment to the surface is loose and disrupted by mi nimal peeling force, In contrast, platelets adhere firmly to intact fi brinogen under the same conditions, suggesting that recognition of con tact sites outside a single D domain can secure the firm interaction n ot supported by a single gamma(400-411) sequence. If platelets are act ivated, the gamma(400-411) sequence is no longer necessary to initiate the adhesion process but becomes sufficient, even as a single copy, t o mediate stable surface attachment in the absence of shear stress, Un der conditions of flow, however, intact fibrinogen but not fragment D can support adhesion, regardless of whether platelets have the potenti al to become activated or not, These results indicate the functional r elevance of multiple fibrinogen domains during the initial stages of t he platelet adhesion process.