Surfactant protein-A enhances respiratory syncytial virus clearance in vivo
Surfactant protein-A enhances respiratory syncytial virus clearance in vivo
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DOI：
10.1172/jci5849
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发表时间：
1999-04-01
影响因子：
15.9
通讯作者：
Korfhagen, T
中科院分区：
文献类型：
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作者：
LeVine, AM;Gwozdz, J;Korfhagen, T
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，通过靶向基因失活产生缺乏SP-A（SP-A（-/-））的小鼠。SP-A（-/-）和对照小鼠（SP-A（+/+））通过气管内滴注感染呼吸道合胞病毒（RSV）。SP-A（-/-）小鼠感染后的肺浸润比SP-A（+/+）小鼠更严重，并与肺匀浆中RSV空斑形成单位增加相关。SP-A（-/-）小鼠中多形核白细胞的肺浸润更大。SP-A（-/-）小鼠肺组织中促炎细胞因子肿瘤坏死因子-α和白细胞介素-6水平升高。RSV感染后，SP-A（-/-）小鼠巨噬细胞中超氧化物和过氧化氢的产生不足，表明SP-A在RSV感染相关的氧化剂产生中起关键作用。RSV与外源性SP-A联合给药可降低SP-A（-/-）小鼠肺中的病毒滴度和炎性细胞。这些发现表明SP-A在体内对RSV起重要的宿主防御作用。
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.