title: Platelet activation and aggregation promote lung inflammation and influenza virus pathogenesis.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  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.
authors: 1 EA4610, Lyon, France.
authors: Vuong Ba
authors: VB
authors: Lê
authors: Jochen G
authors: JG
authors: Schneider
authors: Yvonne
authors: Y
authors: Boergeling
authors: Fatma
authors: F
authors: Berri
authors: Mariette
authors: M
authors: Ducatez
authors: Jean-Luc
authors: JL
authors: Guerin
authors: Iris
authors: I
authors: Adrian
authors: Elisabeth
authors: E
authors: Errazuriz-Cerda
authors: Sonia
authors: S
authors: Frasquilho
authors: Laurent
authors: L
authors: Antunes
authors: Bruno
authors: B
authors: Lina
authors: Jean-Claude
authors: JC
authors: Bordet
authors: Martine
authors: M
authors: Jandrot-Perrus
authors: Stephan
authors: S
authors: Ludwig
authors: Béatrice
authors: B
authors: Riteau
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D000998:Antiviral Agents / Q000627:therapeutic use; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007251:Influenza, Human / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology* / Q000821:virology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009975:Orthomyxoviridae / Q000187:drug effects / Q000472:pathogenicity*; D015539:Platelet Activation / Q000502:physiology*; D010974:Platelet Aggregation / Q000502:physiology*; D011014:Pneumonia / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*
chemical_list: D000893:Anti-Inflammatory Agents; D000998:Antiviral Agents
keywords: flu pathogenesis; lung injury; novel drugs; platelets; pneumonia