title: Amplification of bacteria-induced platelet activation is triggered by FcγRIIA, integrin αIIbβ3, and platelet factor 4.
abstract: Bacterial adhesion to platelets is mediated via a range of strain-specific bacterial surface proteins that bind to a variety of platelet receptors. It is unclear how these interactions lead to platelet activation. We demonstrate a critical role for the immune receptor FcγRIIA, αIIbβ3, and Src and Syk tyrosine kinases in platelet activation by Staphylococcus aureus, Streptococcus sanguinis, Streptococcus gordonii, Streptococcus oralis, and Streptococcus pneumoniae. FcγRIIA activation is dependent on immunoglobulin G (IgG) and αIIbβ3 engagement. Moreover, feedback agonists adenosine 5'-diphosphate and thromboxane A2 are mandatory for platelet aggregation. Additionally, platelet factor 4 (PF4) binds to bacteria and reduces the lag time for aggregation, and gray platelet syndrome α-granule-deficient platelets do not aggregate to 4 of 5 bacterial strains. We propose that FcγRIIA-mediated activation is a common response mechanism used against a wide range of bacteria, and that release of secondary mediators and PF4 serve as a positive feedback mechanism for activation through an IgG-dependent pathway.
authors.affiliation: Centre for Cardiovascular Sciences, Institute of Biomedical Research, School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom;
authors.forename: Mònica
authors.initials: M
authors.lastname: Arman
authors.affiliation: Institut für Immunologie und Transfusionsmedizin, Universitätsmedizin Greifswald, Greifswald, Germany; Zentrum für Innovationskompetenz-Humorale Immunreaktionen bei Kardiovaskulären Erkrankungen, Universitätsmedizin Greifswald, Greifswald, Germany;
authors.forename: Krystin
authors.initials: K
authors.lastname: Krauel
authors.affiliation: Cardiovascular Infection Group, Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland; and.
authors.forename: Dorothea O
authors.initials: DO
authors.lastname: Tilley
authors.affiliation: Abteilung Genetik der Mikroorganismen, Interfakultäres Institut für Genetik und Funktionelle Genomforschung, Ernst-Moritz-Arndt-Universität Greifswald, Greifswald, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Weber
authors.affiliation: Cardiovascular Infection Group, Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland; and.
authors.forename: Dermot
authors.initials: D
authors.lastname: Cox
authors.affiliation: Institut für Immunologie und Transfusionsmedizin, Universitätsmedizin Greifswald, Greifswald, Germany;
authors.forename: Andreas
authors.initials: A
authors.lastname: Greinacher
authors.affiliation: Cardiovascular Infection Group, Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland; and.
authors.forename: Steven W
authors.initials: SW
authors.lastname: Kerrigan
authors.affiliation: Centre for Cardiovascular Sciences, Institute of Biomedical Research, School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom;
authors.forename: Steve P
authors.initials: SP
authors.lastname: Watson
mesh_terms: D000244:Adenosine Diphosphate / Q000276:immunology; D000818:Animals; D001792:Blood Platelets / Q000276:immunology / Q000382:microbiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D015539:Platelet Activation; D010978:Platelet Factor 4 / Q000276:immunology*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000276:immunology*; D017452:Receptors, IgG / Q000276:immunology*; D013203:Staphylococcal Infections / Q000276:immunology; D013211:Staphylococcus aureus / Q000502:physiology*; D013290:Streptococcal Infections / Q000276:immunology; D013291:Streptococcus / Q000502:physiology*; D013928:Thromboxane A2 / Q000276:immunology
chemical_list: C080568:Fc gamma receptor IIA; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D017452:Receptors, IgG; D010978:Platelet Factor 4; D013928:Thromboxane A2; D000244:Adenosine Diphosphate