Acetylsalicylic acid differentially limits the activation and expression of cell death markers in human platelets exposed to Staphylococcus aureus strains

• Published in: Scientific reports Vol. 7; no. 1; pp. 5610 - 16
• Main Authors: Chabert, Adrien, Damien, Pauline, Verhoeven, Paul O, Grattard, Florence, Berthelot, Philippe, Zeni, Fabrice, Panicot-Dubois, Laurence, Robert, Stéphane, Dignat-George, Françoise, Eyraud, Marie-Ange, Pozzetto, Bruno, Payrastre, Bernard, Cognasse, Fabrice, Garraud, Olivier, Hamzeh-Cognasse, Hind
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 17.07.2017; Nature Publishing Group UK; Nature Portfolio
• Subjects: Acetylsalicylic acid; Acids; Apoptosis; Aspirin; Aspirin - pharmacology; Bacteremia; Bacterial Adhesion; Biomarkers - metabolism; Blood Platelets - cytology; Blood Platelets - drug effects; Blood Platelets - physiology; Caspase; Caspase-3; Cell activation; Cell Death; Fluvastatin; Human health and pathology; Humans; Immunology; Infectious diseases; Inflammation; Life Sciences; Membrane potential; Mitochondria; Pathogens; Phosphatidylserine; Platelet Activation - drug effects; Platelet aggregation; Platelet Aggregation - drug effects; Platelet Aggregation Inhibitors - pharmacology; RANTES; Sepsis; Staphylococcal Infections - drug therapy; Staphylococcal Infections - metabolism; Staphylococcal Infections - microbiology; Staphylococcus aureus; Staphylococcus aureus - drug effects; Statins; Strains (organisms); Thrombocytopenia
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-06024-2

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.