Hypersusceptibility to invasive pneumococcal infection in experimental sickle cell disease involves platelet-activating factor receptor.
Children with sickle cell disease have a 600-fold increased incidence of invasive pneumococcal disease. Platelet-activating factor receptor (PAFr) mediates pneumococcal invasion, and up-regulation of PAFr on chronically activated endothelia could contribute to increased bacterial invasion. Mice transplanted with sickle cell bone marrow developed more extensive infection, and 57% died, compared with 16% of wild-type mice. Histopathological analysis revealed that sickle cell mice expressed significantly more PAFr on endothelia and epithelia. Pharmacological blockade or genetic deletion of PAFr protected sickle cell mice from mortality. We conclude that PAFr plays an important role in hypersusceptibility to pneumococcal infection in sickle cell disease.
Miller
Martha L
ML
Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Gao
Geli
G
Pestina
Tamara
T
Persons
Derek
D
Tuomanen
Elaine
E
D000755:Anemia, Sickle Cell / Q000150:complications* / Q000378:metabolism*; D000818:Animals; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D042783:Endothelial Cells / Q000737:chemistry; D004730:Endothelium, Vascular / Q000737:chemistry; D004847:Epithelial Cells / Q000737:chemistry; D007150:Immunohistochemistry; D008168:Lung / Q000098:blood supply / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D010980:Platelet Membrane Glycoproteins / Q000032:analysis / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D011008:Pneumococcal Infections / Q000209:etiology* / Q000378:metabolism*; D011018:Pneumonia, Pneumococcal / Q000209:etiology / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000032:analysis / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D015854:Up-Regulation
D010980:Platelet Membrane Glycoproteins; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor