Hypersusceptibility to Invasive Pneumococcal Infection in Experimental Sickle Cell Disease Involves Platelet-Activating Factor Receptor

• Published in: The Journal of infectious diseases 2007-02, Vol.195 (4), p.581-584
• Main Authors: Miller, Martha L., Gao, Geli, Pestina, Tamara, Persons, Derek, Tuomanen, Elaine
• Format: Article
• Language: English
• Subjects: Anemia, Sickle Cell - complications; Anemia, Sickle Cell - metabolism; Animals; Bacteria; Biological and medical sciences; Disease Models, Animal; Disease risk; Disease Susceptibility; Endothelial Cells - chemistry; Endothelium, Vascular - chemistry; Epidemiology; Epithelial Cells - chemistry; Fundamental and applied biological sciences. Psychology; Immunohistochemistry; Infections; Infectious diseases; Lung - blood supply; Lung - chemistry; Medical sciences; Mice; Mice, Inbred C57BL; Microbiology; Platelet Membrane Glycoproteins - analysis; Platelet Membrane Glycoproteins - antagonists & inhibitors; Platelet Membrane Glycoproteins - biosynthesis; Platelet Membrane Glycoproteins - physiology; Pneumococcal Infections - etiology; Pneumococcal Infections - metabolism; Pneumonia, Pneumococcal - etiology; Pneumonia, Pneumococcal - metabolism; Receptors; Receptors, G-Protein-Coupled - analysis; Receptors, G-Protein-Coupled - antagonists & inhibitors; Receptors, G-Protein-Coupled - biosynthesis; Receptors, G-Protein-Coupled - physiology; Sepsis; Sickle cell disease; Sickles; Streptococcus pneumoniae; Up-Regulation
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/510626

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.