LeVine A M, Gwozdz J, Stark J, Bruno M, Whitsett J, Korfhagen T
Division of Pulmonary Biology, Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA.
J Clin Invest. 1999 Apr;103(7):1015-21. doi: 10.1172/JCI5849.
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-alpha 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.
为了确定表面活性蛋白A（SP-A）在抗病毒宿主防御中的作用，通过靶向基因失活制备了缺乏SP-A的小鼠（SP-A-/-）。通过气管内滴注法将呼吸道合胞病毒（RSV）感染SP-A-/-小鼠和对照小鼠（SP-A+/+）。感染后，SP-A-/-小鼠的肺部浸润比SP-A+/+小鼠更严重，并且与肺匀浆中RSV空斑形成单位的增加有关。SP-A-/-小鼠中多形核白细胞的肺部浸润更严重。SP-A-/-小鼠肺中促炎细胞因子肿瘤坏死因子-α和白细胞介素-6的水平升高。RSV感染后，SP-A-/-小鼠的巨噬细胞中超氧化物和过氧化氢生成不足，表明SP-A在与RSV感染相关的氧化剂产生中起关键作用。将RSV与外源性SP-A共同给药可降低SP-A-/-小鼠肺中的病毒滴度和炎症细胞。这些发现表明，SP-A在体内对RSV起着重要的宿主防御作用。
