Abstract
Objectives: Staphylococcal superantigen-like 5 (SSL5) is an exoprotein secreted by Staphylococcus aureus that has been shown to inhibit neutrophil rolling over activated endothelial cells via a direct interaction with P-selectin glycoprotein ligand 1 (PSGL-1). Methods and Results: When purified recombinant SSL5 was added to washed platelets in an aggregometry set-up, complete and irreversible aggregation was observed. Proteolysis of the extracellular part of GPIbα or the addition of dRGDW abrogated platelet aggregation. When a mixture of isolated platelets and red cells was perfused over immobilized SSL5 at a shear rate of 300 s-1, stable platelet aggregates were observed, and platelet deposition was substantially reduced after proteolysis of GPIb or after addition of dRGDW. SSL5 was shown to interact with glycocalicin, a soluble GPIbα fragment, and binding of SSL5 to platelets resulted in GPIb-mediated signal transduction as evidenced by translocation of 14-3-3ζ. In addition, SSL5 was shown to interact with endothelial cell matrix (ECM) and this interaction enhanced aggregation of platelets from whole blood to this ECM. Conclusions: SSL5 activates and aggregates platelets in a GPIbα-dependent manner, which could be important in colonization of the vascular bed and evasion of the immune system by S. aureus.
Original language | English |
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Pages (from-to) | 1867-1874 |
Number of pages | 8 |
Journal | Journal of Thrombosis and Haemostasis |
Volume | 7 |
Issue number | 11 |
DOIs | |
Publication status | Published - 1 Nov 2009 |
Keywords
- Flow conditions
- GPIbα
- Platelets
- S. aureus
- SSL5