title: Bacillus anthracis peptidoglycan activates human platelets through FcγRII and complement.
abstract: Platelet activation frequently accompanies sepsis and contributes to the sepsis-associated vascular leakage and coagulation dysfunction. Our previous work has implicated peptidoglycan (PGN) as an agent causing systemic inflammation in gram-positive sepsis. We used flow cytometry and fluorescent microscopy to define the effects of PGN on the activation of human platelets. PGN induced platelet aggregation, expression of the activated form of integrin αIIbβ3, and exposure of phosphatidylserine (PS). These changes were dependent on immunoglobulin G and were attenuated by the Fcγ receptor IIa-blocking antibody IV.3, suggesting they are mediated by PGN-anti-PGN immune complexes signaling through Fcγ receptor IIa. PS exposure was not blocked by IV.3 but was sensitive to inhibitors of complement activation. PGN was a potent activator of the complement cascade in human plasma and caused deposition of C5b-9 on the platelet surface. Platelets with exposed PS had greatly accelerated prothrombinase activity. We conclude that PGN derived from gram-positive bacteria is a potent platelet agonist when complexed with anti-PGN antibody and could contribute to the coagulation dysfunction accompanying gram-positive infections.
authors.affiliation: Department of Cell Biology, University of Oklahoma, Oklahoma City, OK, USA.
authors.forename: Dawei
authors.initials: D
authors.lastname: Sun
authors.forename: Narcis I
authors.initials: NI
authors.lastname: Popescu
authors.forename: Brent
authors.initials: B
authors.lastname: Raisley
authors.forename: Ravi S
authors.initials: RS
authors.lastname: Keshari
authors.forename: George L
authors.initials: GL
authors.lastname: Dale
authors.forename: Florea
authors.initials: F
authors.lastname: Lupu
authors.forename: K Mark
authors.initials: KM
authors.lastname: Coggeshall
mesh_terms: D001408:Bacillus anthracis / Q000737:chemistry / Q000276:immunology*; D001792:Blood Platelets / Q000276:immunology; D003165:Complement System Proteins / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007074:Immunoglobulin G / Q000502:physiology; D010457:Peptidoglycan / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D010718:Phosphatidylserines / Q000378:metabolism; D010949:Plasma / Q000378:metabolism / Q000502:physiology; D015539:Platelet Activation / Q000187:drug effects / Q000276:immunology; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism; D011485:Protein Binding; D017452:Receptors, IgG / Q000378:metabolism / Q000502:physiology*
chemical_list: D007074:Immunoglobulin G; D010457:Peptidoglycan; D010718:Phosphatidylserines; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D017452:Receptors, IgG; D003165:Complement System Proteins