thromboxane-a2 and Staphylococcal-Infections

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.

Topics: Adenosine Diphosphate; Animals; Blood Platelets; Host-Pathogen Interactions; Humans; Mice; Mice, Transgenic; Platelet Activation; Platelet Factor 4; Platelet Glycoprotein GPIIb-IIIa Complex; Receptors, IgG; Staphylococcal Infections; Staphylococcus aureus; Streptococcal Infections; Streptococcus; Thromboxane A2