title: Activated platelets mediate Staphylococcus aureus deposition on subendothelial extracellular matrix: the role of glycoprotein Ib.
abstract: Extracellular matrix (ECM) derived from bovine corneal endothelial cells was used as a model to study the role of platelets in Staphylococcus aureus interaction with the vascular subendothelium. In whole blood, S. aureus activated platelets, as demonstrated by P-selectin expression on the platelet membrane. Subjecting platelet-rich plasma (PRP) to the ECM under oscillatory conditions resulted in platelet adhesion and aggregation. S. aureus increased platelet deposition on ECM depending on the bacterium-platelet ratio. Scanning electron microscopy revealed that S. aureus adhered to and formed clusters on ECM-bound platelets. These findings were confirmed by using [3H]thymidine-labeled bacteria that adhered to the surface more extensively after deposition of platelets on ECM. Platelet pre-treatment with prostaglandin E1 resulted in inhibition of bacterial adherence. Glycoprotein (GP)Ib was involved in the bacterium-platelet interaction, as indicated by the following: (i) S. aureus diminished the binding of GPIb but not of GPIX or GPIIb-IIIa monoclonal antibodies (Mab) to washed fixed platelets; (ii) GPIb Mab inhibited S. aureus -induced platelet aggregation in a dose-dependent fashion; (iii) blockade of von Willebrand factor (vWf) binding to GPIb by a recombinant vWf fragment reversed the enhanced platelet deposition on ECM in the presence of S. aureus but did not affect platelet deposition in the absence of bacteria. The results indicate that S. aureus activates platelets and promotes their deposition on ECM via GPIb-dependent mechanism and that adherent platelets mediate S. aureus deposition on the subendothelium. These interactions might play a role in the pathogenesis of bacterial endocarditis.
authors.affiliation: National Hemophilia Center, Institute of Thrombosis and Hemostasis, Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: B
authors.initials: B
authors.lastname: Shenkman
authors.forename: E
authors.initials: E
authors.lastname: Rubinstein
authors.forename: R
authors.initials: R
authors.lastname: Dardik
authors.forename: I
authors.initials: I
authors.lastname: Tamarin
authors.forename: N
authors.initials: N
authors.lastname: Savion
authors.forename: D
authors.initials: D
authors.lastname: Varon