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Am. J. Respir. Cell Mol. Biol., Volume 26, Number 3, March, 2002 277-282

Surfactant Protein-A–Deficient Mice Display an Exaggerated Early Inflammatory Response to a beta -Resistant Strain of Influenza A Virus

Gordon Li, Jiyauddin Siddiqui, Michael Hendry, Jennifer Akiyama, Jess Edmondson, Cynthia Brown, Lennell Allen, Stacey Levitt, Francis Poulain, and Samuel Hawgood

Departments of Pediatrics and Cardiovascular Research Institute, University of California San Francisco, San Francisco, California; and The Viral and Rickettsial Disease Laboratory, California Department of Health Services, Richmond, California

Surfactant protein (SP)-A is a member of the collectin family of proteins. In vitro, SP-A binds influenza A virus (IAV), neutralizes infectivity, and enhances uptake by macrophages. SP-D also binds and neutralizes certain strains of IAV. To determine if SP-A has a role in protecting the intact animal against IAV infection, we inoculated gene-targeted SP-A-deficient mice (-/-) and littermate controls (+/+) with either saline or increasing doses of an IAV strain that binds SP-A but not SP-D. IAV was more virulent in SP-A-/- compared with +/+ mice, with a significantly lower mean lethal dose (LD50) and significantly greater weight loss during infection. SP-A-/- mice also had increased airway epithelial injury and more alveolar cellular infiltrates than +/+ mice. On Day 2, SP-A-/- mice had more neutrophils and higher MIP-2 levels in the lung than +/+ mice. We conclude the altered host response and increased susceptibility to X-79Delta 167 infection in SP-A-/- mice reflects a protective role for SP-A in regulating the host response to IAV. Because the recovery of virus from lung homogenates on Days 2 and 6 after inoculation was comparable in -/- and +/+ mice, we speculate SP-A reduces IAV virulence independently of direct viral neutralization.

Abbreviations: bronchoalveolar lavage, BAL; BAL fluid, BALF; hemagglutinin, HA; influenza A virus, IAV; interferon-gamma , IFN-gamma ; interleukin, IL; mean lethal dose, LD50; macrophage inflammatory protein, MIP; surfactant protein, SP; tumor necrosis factor alpha , TNF-alpha .




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