A role for glycoprotein Ib in Streptococcus sanguis-induced platelet aggregation.
Numerous studies have implicated bacteria in cardiovascular disease, but there is a paucity of information on the mechanism involved. In this study we show how the common oral bacterium Streptococcus sanguis can directly interact with platelets, resulting in activation and aggregate formation. Platelet aggregation was dependent on glycoprotein IIb/IIIa (GPIIb/IIIa) and thromboxane. Platelets could also directly bind to S sanguis, but this interaction was not inhibited by GPIIb/IIIa antagonists. Antibodies to GPIb could inhibit both platelet aggregation and platelet adhesion to bacteria. This suggested a direct interaction between GPIb and S sanguis; however, this interaction did not require von Willebrand factor, the normal ligand for GPIb. By use of a range of monoclonal antibodies to GPIb and the enzyme mocharagin, which cleaves GPIb at amino acid 282, the interaction was localized to a region within the N-terminal 1-225 portion of GPIbalpha. Furthermore S sanguis failed to induce aggregation of platelets from a patient with Bernard-Soulier disease, the organism bound to Chinese hamster ovary cells transfected with the GPIbalpha gene but did not bind to mock-transfected cells and biotin-labeled S sanguis cells bound to purified GPIb in ligand blots. It is suggested that the interaction between S sanguis and GPIb is important in the pathogenesis of infective endocarditis and may also play a contributory role in some cases of myocardial infarction.
Kerrigan
Steven W
SW
Department of Clinical Pharmacology, Royal College of Surgeons in Ireland, Dublin, Ireland.
Douglas
Ian
I
Wray
Ann
A
Heath
Jason
J
Byrne
Michael F
MF
Fitzgerald
Desmond
D
Cox
Dermot
D
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000378:metabolism / Q000502:physiology; D001665:Binding Sites; D002448:Cell Adhesion / Q000187:drug effects; D004697:Endocarditis, Bacterial / Q000209:etiology / Q000382:microbiology; D006801:Humans; D010974:Platelet Aggregation; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000494:pharmacology; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D011485:Protein Binding; D017452:Receptors, IgG / Q000378:metabolism / Q000502:physiology; D013298:Streptococcus sanguis / Q000166:cytology / Q000472:pathogenicity*; D014841:von Willebrand Factor / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C080568:Fc gamma receptor IIA; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D019038:Platelet Glycoprotein GPIb-IX Complex; D017452:Receptors, IgG; D014841:von Willebrand Factor