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 1

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Pulmonary pathology after RSV infection. Photomicrographs of lung parenc...
Pulmonary pathology after RSV infection. Photomicrographs of lung parenchyma in (a) SP-A–/– and (b) SP-A+/+ mice were prepared 7 days after intratracheal administration of 107 pfu RSV. Histological sections were stained with hematoxylin and eosin. Infiltration was observed surrounding the terminal bronchi and pulmonary vessels in the SP-A–/– and SP-A+/+ mice. Higher magnification demonstrates infiltration with mononuclear cells and polymorphonuclear leukocytes in SP-A–/– mice (c). Cells from BAL consisted of mononuclear cells (arrowhead) and polymorphonuclear leukocytes (arrow) (d). a and b: ×10; c and d: ×40. BAL, bronchoalveolar lavage; pfu, plaque-forming units; RSV, respiratory syncytial virus; SP-A, surfactant protein-A.