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* Cardiovascular Research Institute, University of California, San Francisco, CA 94143; and
Microbial Pathogenesis and Host Defense, Genentech Hall, University of California, San Francisco, CA 94158
CD47 modulates neutrophil transmigration toward the sites of infection or injury. Mice lacking CD47 are susceptible to Escherichia coli (E. coli) peritonitis. However, less is known concerning the role of CD47 in the development of acute lung inflammation and injury. In this study, we show that mice lacking CD47 are protected from LPS-induced acute lung injury and E. coli pneumonia with a significant reduction in pulmonary edema, lung vascular permeability, and bacteremia. Reconstitution of CD47+/– mice with CD47–/– neutrophils significantly reduced lung edema and neutrophil infiltration, thus demonstrating that CD47+ neutrophils are required for the development of lung injury from E. coli pneumonia. Importantly, CD47-deficient mice with E. coli pneumonia had an improved survival rate. Taken together, deficiency of CD47 protects mice from LPS-induced acute lung injury and E. coli pneumonia. Targeting CD47 may be a novel pathway for treatment of acute lung injury.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This study was supported by National Heart, Lung, and Blood Institute Grants HL-51854 and HL-51856 (to M.A.M.), National Institutes of Health Grants R01 GM38330 and P01 AI53194 (to E.J.B.), and National Heart, Lung, and Blood Institute K08 HL-82742 Award (to M.R.L.).
2 Address correspondence and reprint requests to Dr. Xiao Su, Cardiovascular Research Institute, University of California San Francisco, Health Science West 825, 505 Parnassus Avenue, San Francisco, CA 94143. E-mail address: suxiao{at}yahoo.com
3 Abbreviations used in this paper: PMN, polymorphonuclear leukocyte; WT, wild type; BAL, bronchoalveolar lavage; MPO, myeloperoxidase.
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