Surfactant protein-A enhances respiratory syncytial virus clearance in vivo

To determine the role of surfactant protein-A(SP-A) in antiviral host defen se, mice lacking SP-A (SP-A(-/-)) were produced by targeted gene inactivati on. SP-A(-/-) and control mice (SP-A(+/+)) were infected with respiratory s yncytial 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. Pu lmonary infiltration with polymorphonuclear leukocytes was greater in the S P-A(-/-) mice. Levels of proinflammatory cytokines tumor necrosis factor-al pha and interleukin-6 were enhanced in lungs of SP-A(-/-) mice. After RSV i nfection, superoxide and hydrogen peroxide generation was deficient in macr ophages from SP-A(-/-) mice, demonstrating a critical role of SP-A in oxida nt production associated with RSV infection. Coadministration of RSV with e xogenous 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.