title: The role of immunoglobulin G and fibrinogen in platelet aggregation by Streptococcus sanguis.
abstract: Previous work has shown that the type strain of Streptococcus sanguis, NCTC 7863, induces aggregation of normal platelets by a complement-dependent mechanism. We investigated the roles of IgG and fibrinogen in the aggregation process. Plasma depleted of IgG by passage through protein A-sepharose failed to support platelet aggregation, as did plasma absorbed at 0 degrees C with whole bacteria. However, absorption of plasma with a non-aggregating strain of S. sanguis, SK96, did not remove aggregating activity for NCTC 7863. Supplementing 0 degrees C-absorbed plasma with purified IgG restored the aggregation supporting activity. A monoclonal antibody to the Fc gammaRII receptor inhibited platelet aggregation by the bacteria, indicating a requirement for bacteria-IgG complexes interacting with the Fc receptor in platelet aggregation. There was a lag time to the onset of platelet aggregation of 7-19 min depending upon the platelet donor, but the length of this lag did not correlate with either total IgG concentration recognizing NCTC 7863 in subjects' plasma, or the concentration any of the four IgG subclasses or with IgG avidity levels. Fibrinogen was shown to bind rapidly to the bacterial cell surface. Monoclonal antibody to GPIIb/IIIa, RGDS peptide, and a specific antagonist for the platelet fibrinogen receptor, GPIIb/IIIa, FK633, inhibited platelet aggregation by NCTC 7863, indicating that platelet aggregation is fibrinogen dependent. These data suggest that platelet aggregation by some strains of S. sanguis requires multiple stimuli/agonists, including IgG-Fc receptor interaction, complement and fibrinogen.
authors.affiliation: Department of Haematology, Royal Hallamshire Hospital, School of Clinical Dentistry, University of Sheffield.
authors.forename: I
authors.initials: I
authors.lastname: Ford
authors.forename: C W
authors.initials: CW
authors.lastname: Douglas
authors.forename: D
authors.initials: D
authors.lastname: Cox
authors.forename: D G
authors.initials: DG
authors.lastname: Rees
authors.forename: J
authors.initials: J
authors.lastname: Heath
authors.forename: F E
authors.initials: FE
authors.lastname: Preston
mesh_terms: D003165:Complement System Proteins; D005340:Fibrinogen / Q000502:physiology*; D005434:Flow Cytometry; D006801:Humans; D007074:Immunoglobulin G / Q000502:physiology*; D010974:Platelet Aggregation / Q000502:physiology*; D017452:Receptors, IgG / Q000502:physiology; D013298:Streptococcus sanguis / Q000502:physiology*
chemical_list: D007074:Immunoglobulin G; D017452:Receptors, IgG; D005340:Fibrinogen; D003165:Complement System Proteins