Surfactant protein-A enhances respiratory syncytial virus clearance in vivo
Ann Marie LeVine, … , Jeffrey Whitsett, Thomas Korfhagen
Ann Marie LeVine, … , Jeffrey Whitsett, Thomas Korfhagen
Published April 1, 1999
Citation Information: J Clin Invest. 1999;103(7):1015-1021. https://doi.org/10.1172/JCI5849.
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Article

Surfactant protein-A enhances respiratory syncytial virus clearance in vivo

Abstract

To determine the role of surfactant protein-A(SP-A) in antiviral host defense, mice lacking SP-A (SP-A–/–) were produced by targeted gene inactivation. SP-A–/– and control mice (SP-A+/+) were infected with respiratory syncytial virus (RSV) by intratracheal instillation. Pulmonary infiltration after infection was more severe in SP-A–/– than in SP-A+/+ mice and was associated with increased RSV plaque-forming units in lung homogenates. Pulmonary infiltration with polymorphonuclear leukocytes was greater in the SP-A–/– mice. Levels of proinflammatory cytokines tumor necrosis factor-α and interleukin-6 were enhanced in lungs of SP-A–/– mice. After RSV infection, superoxide and hydrogen peroxide generation was deficient in macrophages from SP-A–/– mice, demonstrating a critical role of SP-A in oxidant production associated with RSV infection. Coadministration of RSV with exogenous SP-A reduced viral titers and inflammatory cells in the lung of SP-A–/– mice. These findings demonstrate that SP-A plays an important host defense role against RSV in vivo.

Authors

Ann Marie LeVine, Jodie Gwozdz, James Stark, Michael Bruno, Jeffrey Whitsett, Thomas Korfhagen

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Increased total cell counts in BAL fluid from SP-A–/– mice. Lung cells w...
Increased total cell counts in BAL fluid from SP-A–/– mice. Lung cells were recovered by BAL, stained with trypan blue, and counted under light microscopy. (a) The low dose of RSV (106 pfu) caused less migration of inflammatory cells in the lungs from both genotypes; however, an earlier influx of cells was found in SP-A–/– (filled bars) BAL fluid than in SP-A+/+ (hatched bars) mice. (b) SP-A–/– mice infected with 107 pfu RSV had significantly greater total cell counts in BAL fluid at all time points. Data are mean ± SEM with n = 5 mice per group (a) and n = 9 mice per group (b). *P < 0.05 compared with SP-A+/+ mice.