Abstract
Beyond their hemostatic functions, platelets alter their inflammatory response according to the bacterial stimulus. Staphylococcus aureus is associated with exacerbated inflammation and thrombocytopenia, which is associated with poor prognosis during sepsis. Acetylsalicylic acid and statins prevent platelet aggregation and decrease the mortality rate during sepsis. Therefore, we assessed whether these two molecules could reduce in vitro platelet activation and the inflammatory response to S. aureus. Platelets were exposed to clinical strains of S. aureus in the presence or absence of acetylsalicylic acid or fluvastatin. Platelet activation, aggregation, and release of soluble sCD62P, sCD40 Ligand, RANTES and GROα were assessed. Platelet cell death was evaluated by analyzing the mitochondrial membrane potential, phosphatidylserine exposure, platelet microparticle release and caspase-3 activation. All S. aureus strains induced platelet activation but not aggregation and decreased the platelet count, the expression of cell death markers and the release of RANTES and GROα. Acetylsalicylic acid but not fluvastatin limited platelet activation and inflammatory factor release and restored the platelet count by protecting platelets from Staphylococcus-induced expression of cell death markers. This study demonstrates that acetylsalicylic acid limits S. aureus-induced effects on platelets by reducing cell death, revealing new strategies to reduce the platelet contribution to bacteremia-associated inflammation.
Highlights
Beyond their hemostatic functions, platelets alter their inflammatory response according to the bacterial stimulus
We observed that S. condimenti did not affect the platelet counts compared with the controls (146.3 ± 15.6 × 106 Pl/ml vs. 163.2 ± 5.3 × 106 Pl/ml, respectively, p > 0.05)
All clinical S. aureus strains isolated from bacteremia (SaB) drastically and significantly reduced platelet counts (p < 0.001) comparably to the effects of Thrombin receptor activator peptide (TRAP)-stimulation (Fig. 1)
Summary
Platelets alter their inflammatory response according to the bacterial stimulus. All S. aureus strains induced platelet activation but not aggregation and decreased the platelet count, the expression of cell death markers and the release of RANTES and GROα. Acetylsalicylic acid but not fluvastatin limited platelet activation and inflammatory factor release and restored the platelet count by protecting platelets from Staphylococcus-induced expression of cell death markers. This study demonstrates that acetylsalicylic acid limits S. aureus-induced effects on platelets by reducing cell death, revealing new strategies to reduce the platelet contribution to bacteremia-associated inflammation. Sepsis is frequently accompanied by thrombocytopenia; a previous study showed that the latter follows the course of bloodstream infection and parallels adverse outcomes[21] These findings collectively suggest that platelets have a crucial role in the pathophysiology of sepsis[22, 23]. S. aureus has been shown to induce (in vitro) the degradation of the survival protein Bcl-xL, indicating that this bacterium triggers platelet apoptosis[29]
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