Platelet activation and aggregation promote lung inflammation and influenza virus pathogenesis

Vuong Ba Lê, Jochen G. Schneider, Yvonne Boergeling, Fatma Berri, Mariette Ducatez, Jean Luc Guerin, Iris Adrian, Elisabeth Errazuriz-Cerda, Sonia Frasquilho, Laurent Antunes, Bruno Lina, Jean Claude Bordet, Martine Jandrot-Perrus, Stephan Ludwig, Bé Atrice Riteau*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

104 Citations (Scopus)

Abstract

Rationale: The hallmark of severe influenza virus infection is excessive inflammation of the lungs. Platelets are activated during influenza, but their role in influenza virus pathogenesis and inflammatory responses is unknown. Objectives: To determine the role of platelets during influenza A virus infections and propose new therapeutics against influenza. Methods: We used targeted gene deletion approaches and pharmacologic interventions to investigate the role of platelets during influenza virus infection in mice. Measurements and Main Results: Lungs of infected mice were massively infiltrated by aggregates of activated platelets. Platelet activation promoted influenza A virus pathogenesis. Activating protease-activated receptor 4, a platelet receptor for thrombin that is crucial for platelet activation, exacerbated influenza-induced acute lung injury and death. In contrast, deficiency in the major platelet receptor glycoprotein IIIa protected mice from death caused by influenza viruses, and treating the mice with a specific glycoprotein IIb/IIIa antagonist, eptifibatide, had the same effect. Interestingly, mice treated with other antiplatelet compounds (antagonists of protease-activated receptor 4, MRS 2179, and clopidogrel) were also protected from severe lung injury and lethal infections induced by several influenza strains. Conclusions: The intricate relationship between hemostasis and inflammation has major consequences in influenza virus pathogenesis, and antiplatelet drugs might be explored to develop new antiinflammatory treatment against influenza virus infections.

Original languageEnglish
Pages (from-to)804-819
Number of pages16
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume191
Issue number7
DOIs
Publication statusPublished - 1 Apr 2015

Keywords

  • Flu pathogenesis
  • Lung injury
  • Novel drugs
  • Platelets
  • Pneumonia

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