Abstract
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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Anemia, Sickle Cell / complications*
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Anemia, Sickle Cell / metabolism*
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Animals
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Disease Models, Animal
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Disease Susceptibility*
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Endothelial Cells / chemistry
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Endothelium, Vascular / chemistry
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Epithelial Cells / chemistry
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Immunohistochemistry
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Lung / blood supply
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Lung / chemistry
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Mice
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Mice, Inbred C57BL
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Platelet Membrane Glycoproteins / analysis
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Platelet Membrane Glycoproteins / antagonists & inhibitors
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Platelet Membrane Glycoproteins / biosynthesis
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Platelet Membrane Glycoproteins / physiology*
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Pneumococcal Infections / etiology*
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Pneumococcal Infections / metabolism*
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Pneumonia, Pneumococcal / etiology
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Pneumonia, Pneumococcal / metabolism
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Receptors, G-Protein-Coupled / analysis
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Receptors, G-Protein-Coupled / antagonists & inhibitors
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Receptors, G-Protein-Coupled / biosynthesis
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Receptors, G-Protein-Coupled / physiology*
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Up-Regulation
Substances
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Platelet Membrane Glycoproteins
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Receptors, G-Protein-Coupled
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platelet activating factor receptor