title: Escherichia coli induces platelet aggregation in an FcγRIIa-dependent manner.
abstract: BACKGROUND
  The discovery of pathogen-recognition receptors such as Toll-like receptors on platelets has led to the emergence of the concept of platelets as important components of the host response to infection. Escherichia coli (E. coli)-mediated sepsis is a serious illness characterized by the occurrence of thrombocytopenia. Whereas there has been a wealth of research on platelet activation by Gram-positive bacteria, little is known about the mechanisms associated with Gram-negative bacteria-induced platelet activation with Gram-negative bacteria.
  
  
  OBJECTIVE
  To determine the mechanisms by which Gram-negative E. coli induces platelet aggregation.
  
  
  METHODS
  Induction of platelet aggregation with E. coli strain O157:H7 was tested in platelet-rich plasma (PRP), washed platelets, and serum depleted of complement factors. Platelet inhibitors (against αII b β3 , glycoprotein Ibα and FcγRIIa) were used. Platelet thromboxane synthesis was analyzed after E. coli stimulation. Cell binding assays were used to assess the ability of E. coli to support platelet adhesion. Trypsinization was used to determine the role of E. coli surface proteins.
  
  
  CONCLUSIONS
  E. coli-induced aggregation in PRP was donor-dependent. E. coli O157:H7 induced aggregation with a lag time of 6.9 ± 1.3 min in an αII b β3 -dependent and FcγRIIa-dependent manner. Furthermore, this interaction was enhanced by the presence of complement, and was dependent on thromboxane synthesis. These results show E. coli to be a potent inducer of platelet aggregation.
authors.affiliation: Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland.
authors.forename: R D
authors.initials: RD
authors.lastname: Moriarty
authors.affiliation: Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland.
authors.forename: A
authors.initials: A
authors.lastname: Cox
authors.affiliation: Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland.
authors.forename: M
authors.initials: M
authors.lastname: McCall
authors.affiliation: Department of Clinical Microbiology, School of Medicine, Trinity College Dublin, Dublin, Ireland.
authors.forename: S G J
authors.initials: SG
authors.lastname: Smith
authors.affiliation: Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland.
authors.forename: D
authors.initials: D
authors.lastname: Cox
mesh_terms: D001792:Blood Platelets / Q000276:immunology; D002462:Cell Membrane / Q000382:microbiology; D004927:Escherichia coli Infections / Q000097:blood; D019453:Escherichia coli O157 / Q000472:pathogenicity*; D006801:Humans; D015539:Platelet Activation; D010973:Platelet Adhesiveness; D010974:Platelet Aggregation; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry; D010979:Platelet Function Tests; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000276:immunology; D053657:Platelet-Rich Plasma / Q000378:metabolism; D017452:Receptors, IgG / Q000737:chemistry*; D018805:Sepsis / Q000503:physiopathology; D013921:Thrombocytopenia / Q000276:immunology*; D013929:Thromboxane B2 / Q000737:chemistry
chemical_list: C080568:Fc gamma receptor IIA; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D017452:Receptors, IgG; D013929:Thromboxane B2
keywords: Escherichia coli; FcγRIIa; blood platelets; complement system proteins; sepsis