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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Figure 7

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SP-A decreased inflammatory cells in BAL fluid from SP-A–/– mice. After ...
SP-A decreased inflammatory cells in BAL fluid from SP-A–/– mice. After RSV infection (107 pfu), lung cells were recovered by BAL, stained with trypan blue, and counted under light microscopy. One and 3 days after RSV infection, total cell counts in BAL fluid were significantly reduced in SP-A–/– mice treated with SP-A (100 μg) (cross-hatched bars) compared with untreated SP-A–/– mice (filled bars). Treatment of SP-A–/– mice reduced BAL cell counts to the wild-type level (hatched bars). Total cell counts in BAL fluid were similar in SP-A–treated (open bars) and untreated wild-type mice (hatched bars). Data are mean ± SEM. *P < 0.05 compared with SP-A+/+ mice.