title: 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.
authors.affiliation: Laboratory of Experimental Internal Medicine and Department of Internal Medicine, Academic Medical Center, University of Amsterdam, F4-105, Meibergdreef 9, 1105-AZ Amsterdam, The Netherlands. a.w.rijneveld@amc.uva.nl
authors.forename: Anita W
authors.initials: AW
authors.lastname: Rijneveld
authors.forename: Sebastiaan
authors.initials: S
authors.lastname: Weijer
authors.forename: Sandrine
authors.initials: S
authors.lastname: Florquin
authors.forename: Peter
authors.initials: P
authors.lastname: Speelman
authors.forename: Takao
authors.initials: T
authors.lastname: Shimizu
authors.forename: Satosh
authors.initials: S
authors.lastname: Ishii
authors.forename: Tom
authors.initials: T
authors.lastname: van der Poll
mesh_terms: D000818:Animals; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D005260:Female; D007249:Inflammation; D007958:Leukocyte Count; D008168:Lung / Q000382:microbiology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010980:Platelet Membrane Glycoproteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D011018:Pneumonia, Pneumococcal / Q000276:immunology* / Q000473:pathology; D043562:Receptors, G-Protein-Coupled / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D013296:Streptococcus pneumoniae / Q000302:isolation & purification; D013534:Survival; D013997:Time Factors
chemical_list: D010980:Platelet Membrane Glycoproteins; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor