title: Thrombocytopenia impairs host defense during murine Streptococcus pneumoniae pneumonia.
abstract: OBJECTIVE
  Streptococcus pneumoniae is the most common causative pathogen in community-acquired pneumonia. In patients, thrombocytopenia is correlated with an adverse outcome of pneumonia. Platelets can modulate the host response to infection in several ways, that is, by facilitating clot formation, production of antimicrobial proteins, and interaction with neutrophils. We studied the effect of thrombocytopenia during murine pneumococcal pneumonia.
  
  
  METHODS
  Animal study.
  
  
  METHODS
  University research laboratory.
  
  
  METHODS
  Mice.
  
  
  METHODS
  Pneumonia was induced by intranasal inoculation of S. pneumoniae. Platelets were depleted by anti-mouse thrombocyte serum; controls received nonimmunogenic serum. In separate studies, mice were treated with the platelet P2Y12 receptor inhibitor clopidogrel or placebo.
  
  
  RESULTS
  Thrombocytopenic mice (platelet counts < 1% of uninfected controls) showed a reduced survival during pneumococcal pneumonia (27% vs 75% among controls; p = 0.003), which was associated with higher bacterial loads in lungs, spleen, and blood. Thrombocytopenic mice showed enhanced coagulation activation (thrombin-antithrombin complexes) in plasma. Proinflammatory cytokine levels were higher in plasma but not in lungs of thrombocytopenic mice. Although clopidogrel treatment strongly prolonged the bleeding time, it did not impact on bacterial loads during pneumococcal pneumonia.
  
  
  CONCLUSIONS
  Platelets play a protective role during pneumococcal pneumonia independent of their aggregation.
authors: 1Center for Experimental and Molecular Medicine (CEMM), Academic Medical Center, Amsterdam, The Netherlands. 2Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, Amsterdam, The Netherlands. 3Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands. 4Department of Intensive Care Medicine, Academic Medical Center, Amsterdam, The Netherlands. 5Laboratory of Experimental Intensive Care and Anesthesiology (LEICA), Academic Medical Center, Amsterdam, The Netherlands. 6Division of Infectious Diseases, Academic Medical Center, Amsterdam, The Netherlands.
authors: Florry E
authors: FE
authors: van den Boogaard
authors: Marcel
authors: M
authors: Schouten
authors: Sacha F
authors: SF
authors: de Stoppelaar
authors: Joris J T H
authors: JJ
authors: Roelofs
authors: Xanthe
authors: X
authors: Brands
authors: Marcus J
authors: MJ
authors: Schultz
authors: Cornelis
authors: C
authors: van't Veer
authors: Tom
authors: T
authors: van der Poll
mesh_terms: D000818:Animals; D000990:Antithrombin III / Q000378:metabolism; D000077144:Clopidogrel; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D051379:Mice; D010447:Peptide Hydrolases / Q000378:metabolism; D011018:Pneumonia, Pneumococcal / Q000453:epidemiology / Q000276:immunology* / Q000473:pathology; D058921:Purinergic P2Y Receptor Antagonists / Q000494:pharmacology; D013296:Streptococcus pneumoniae; D013921:Thrombocytopenia / Q000453:epidemiology / Q000276:immunology* / Q000473:pathology; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D016207:Cytokines; D058921:Purinergic P2Y Receptor Antagonists; C046193:antithrombin III-protease complex; D000990:Antithrombin III; D000077144:Clopidogrel; D010447:Peptide Hydrolases; D013988:Ticlopidine