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Improved host defense against pneumococcal pneumonia in platelet-activating factor receptor-deficient mice.

Abstract
Platelet-activating factor (PAF) is a phospholipid with proinflammatory properties that binds to a specific receptor (PAF receptor [PAFR]) that is expressed on many different cell types. PAFR is able to bind phosphorylcholine, which is present in both PAF and the pneumococcal cell wall. Activation of respiratory epithelial cells in vitro results in up-regulation of PAFR, which, in turn, facilitates invasion of Streptococcus pneumoniae. To determine the role of PAFR in host defense against pneumococcal pneumonia, PAFR-deficient (PAFR(-/-)) and wild-type (wt) mice were inoculated intranasally with S. pneumoniae. PAFR(-/-) mice were relatively resistant to pneumococcal pneumonia, as indicated by delayed and reduced mortality, diminished outgrowth of pneumococci in lungs, and reduced dissemination of the infection (all P<.05, vs. wt mice). PAFR(-/-) mice also had less pulmonary inflammation. These data provide evidence that PAFR is used by S. pneumoniae to induce lethal pneumonia.
AuthorsAnita W Rijneveld, Sebastiaan Weijer, Sandrine Florquin, Peter Speelman, Takao Shimizu, Satosh Ishii, Tom van der Poll
JournalThe Journal of infectious diseases (J Infect Dis) Vol. 189 Issue 4 Pg. 711-6 (Feb 15 2004) ISSN: 0022-1899 [Print] United States
PMID14767826 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Platelet Membrane Glycoproteins
  • Receptors, G-Protein-Coupled
  • platelet activating factor receptor
Topics
  • Animals
  • Crosses, Genetic
  • Disease Models, Animal
  • Female
  • Inflammation
  • Leukocyte Count
  • Lung (microbiology, pathology)
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Platelet Membrane Glycoproteins (deficiency, genetics, physiology)
  • Pneumonia, Pneumococcal (immunology, pathology)
  • Receptors, G-Protein-Coupled (deficiency, genetics, physiology)
  • Streptococcus pneumoniae (isolation & purification)
  • Survival
  • Time Factors

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