Investigation of alternative mechanisms of collagen-induced platelet activation by using monoclonal antibodies to glycoprotein IIb-IIIa and fibrinogen.
Anti-HuPl-ml (reactive with IIIa) and anti-C2G7 (reactive with the carboxyl terminal of the alpha chain of fibrinogen) were used to investigate platelet aggregation, fibrinogen binding and thromboxane synthesis induced by low dose collagen (LDC) or high dose collagen (HDC) in normal or aspirin treated platelets. Anti-HuPl-ml and anti-C2G7 inhibited LDC induced platelet aggregation almost completely whilst abolishing fibrinogen binding; thromboxane production although reduced, still occurred. Thus LDC activation was dependent on fibrinogen binding to Gp IIIa. Aggregation of platelets induced by HDC was inhibited with anti-C2G7 or anti-HuPl-ml by 15-35% in association with a modest reduction in thromboxane (TxB2) production (with anti-HuPl-ml) and total inhibition of fibrinogen binding. When anti-HuPl-ml was added to aspirin treated platelets, aggregation with HDC although substantially reduced was not totally abolished. Collagen appears to activate platelets in a dose related manner in which there are at least three possible mechanisms via: (i) GpIIb-IIIa and associated fibrinogen binding; (ii) prostaglandin pathway; (iii) an alternate pathway responsible for approximately 20%-30% of platelet aggregation.
D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D003094:Collagen / Q000494:pharmacology* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005340:Fibrinogen / Q000276:immunology / Q000502:physiology*; D006023:Glycoproteins / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007457:Iodine Radioisotopes; D008565:Membrane Proteins / Q000276:immunology / Q000502:physiology*; D010974:Platelet Aggregation / Q000187:drug effects*; D010980:Platelet Membrane Glycoproteins; D011485:Protein Binding; D013329:Structure-Activity Relationship; D013929:Thromboxane B2 / Q000378:metabolism
D000911:Antibodies, Monoclonal; D006023:Glycoproteins; D007457:Iodine Radioisotopes; D008565:Membrane Proteins; D010980:Platelet Membrane Glycoproteins; D013929:Thromboxane B2; D005340:Fibrinogen; D003094:Collagen; D001241:Aspirin