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Published ahead of print on March 11, 2004, doi:10.1165/rcmb.2003-0107OC
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American Journal of Respiratory Cell and Molecular Biology. Vol. 31, pp. 193-199, 2004
© 2004 American Thoracic Society
DOI: 10.1165/rcmb.2003-0107OC

Surfactant Protein-D Enhances Phagocytosis and Pulmonary Clearance of Respiratory Syncytial Virus

Ann Marie LeVine, James Elliott, Jeffrey A. Whitsett, Anon Srikiatkhachorn, Erika Crouch, Nihal DeSilva and Thomas Korfhagen

Divisions of Pulmonary Biology, Critical Care Medicine, and Pulmonary Medicine, Allergy, and Clinical Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; and Department of Pathology, Washington University School of Medicine, St. Louis, Missouri

Address correspondence to: Ann Marie LeVine, M.D., Cincinnati Children's Hospital Medical Center, Division of Pulmonary Biology and Critical Care Medicine, 3333 Burnet Avenue, Cincinnati, OH 45229-3039. E-mail: annmarie.levine{at}cchmc.org

Surfactant protein (SP)-D gene targeted (SP-D–/–) and wild-type mice were infected with respiratory syncytial virus (RSV) by intratracheal instillation. Decreased clearance of RSV was observed in SP-D–/– mice. Deficiency of SP-D was associated with increased inflammation and inflammatory cell recruitment in the lung after infection. In vitro, SP-D bound RSV-infected Vero cells. Binding was inhibited with ethylenediamine tetraacetic acid and maltose, suggesting that the carbohydrate recognition domain of SP-D recognizes RSV glycoproteins in a calcium-dependent manner. SP-D bound specifically to the RSV proteins G and F. Phagocytosis of RSV by alveolar macrophages was reduced in the absence of SP-D in vivo, and SP-D enhanced phagocytosis of RSV by alveolar macrophages and neutrophils but not peritoneal macrophages in vitro. Oxygen radical production by alveolar macrophages from SP-D+/+ and SP-D–/– mice was decreased after RSV infection, and SP-D ameliorated the inhibitory effects of RSV on oxygen radical production by macrophages and neutrophils in vitro. Because the airway is the usual portal of entry for RSV and other respiratory pathogens, the local production of SP-D is likely to play a role in innate defense responses to inhaled viruses.

Abbreviations: bronchoalveolar lavage, BAL • BAL fluid, BALF • carbohydrate recognition domain, CRD • 2,7 dichlorofluorescin diacetate, DCF • ethylenediamine tetraacetic acid, EDTA • enzyme-linked immunosorbent assay, ELISA • Eagle's minimal essential media, EMEM • fluorescein isothiocyanate, FITC • influenza A virus, IAV • interferon-{gamma}, IFN-{gamma} • macrophage inflammatory protein, MIP • phosphate-buffered saline, PBS • respiratory syncytial virus, RSV • surfactant protein, SP • tumor necrosis factor-{alpha}, TNF-{alpha}




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