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 function influences the mechanisms that initiate platelet thrombus formation onto surface-bound fibrinogen and isolated fibrinogen domains. Under stationary conditions and with full activation of platelets blocked by prostaglandin E1, the carboxyl-terminal gamma 400-411 sequence is necessary for establishing initial contact with the immobilized substrate. Molecules containing a single copy of this sequence, like the plasmin-generated fibrinogen fragment D, support platelet spreading, but the resulting attachment to the surface is loose and disrupted by minimal peeling force. In contrast, platelets adhere firmly to intact fibrinogen under the same conditions, suggesting that recognition of contact sites outside a single D domain can secure the firm interaction not supported by a single gamma 400-411 sequence. If platelets are activated, the gamma 400-411 sequence is no longer necessary to initiate the adhesion process but becomes sufficient, even as a single copy, to mediate stable surface attachment in the absence of shear stress. Under conditions of flow, however, intact fibrinogen but not fragment D can support adhesion, regardless of whether platelets have the potential to become activated or not. These results indicate the functional relevance of multiple fibrinogen domains during the initial stages of the platelet adhesion process.
D000527:Alprostadil / Q000494:pharmacology; D000595:Amino Acid Sequence; D001792:Blood Platelets / Q000166:cytology* / Q000187:drug effects / Q000648:ultrastructure; D002448:Cell Adhesion; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005340:Fibrinogen / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008855:Microscopy, Electron, Scanning; D008969:Molecular Sequence Data; D015539:Platelet Activation; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism*; D011485:Protein Binding
D005338:Fibrin Fibrinogen Degradation Products; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; C015214:fibrinogen D fragment; D005340:Fibrinogen; D000527:Alprostadil