Improved host defense against pneumococcal pneumonia in platelet-activating factor receptor-deficient mice.
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.
Rijneveld
Anita W
AW
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
Weijer
Sebastiaan
S
Florquin
Sandrine
S
Speelman
Peter
P
Shimizu
Takao
T
Ishii
Satosh
S
van der Poll
Tom
T
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
D010980:Platelet Membrane Glycoproteins; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor