Surfactant-associated protein A inhibits LPS-induced cytokine and nitric oxide production in vivo
Surfactant-associated protein A inhibits LPS-induced cytokine and nitric oxide production in vivo
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DOI：
10.1152/ajplung.2000.278.4.l840
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发表时间：
2000-04-01
影响因子：
4.9
通讯作者：
Wright, JR
中科院分区：
文献类型：
--
作者：
Borron, P;McIntosh, JC;Wright, JR
用SP-A基因靶向[SP-deficient; SP-A（-/-）]和野生型[SP-A（+/+）]小鼠体内评估了表面活性物质相关蛋白（SP）A在介导细菌脂多糖（LPS）肺反应中的作用。在气管内给予LPS后，测定回收的支气管肺泡灌洗液中肿瘤坏死因子（TNF）或巨噬细胞炎性蛋白-2和一氧化氮的浓度。LPS处理后，SP-A（-/-）小鼠比SP-A（+/+）小鼠产生显著更多的TNF-α和一氧化氮。对SP-A（-/-）小鼠腹腔注射人SP-A（1 mg/kg）后，TNF-α、巨噬细胞炎性蛋白-2和一氧化氮的产生恢复到SP-A（+/+）小鼠的水平。肺损伤的其他标志物，包括支气管肺泡液蛋白、磷脂含量和中性粒细胞数量不受SP-A的影响。来自旨在测试SP-A介导的抑制的可能机制的实验的数据表明，SP-A与LPS的结合和增强的LPS清除都不是抑制的主要手段。我们的数据和其他数据表明，SP-A直接作用于免疫细胞，以抑制LPS诱导的炎症。这些结果表明，内源性或外源性SP-A抑制体内肺LPS诱导的细胞因子和一氧化氮的产生。
The role of surfactant-associated protein (SP) A in the mediation of pulmonary responses to bacterial lipopolysaccharide (LPS) was assessed in vivo with SP-A gene-targeted [SP-deficient; SP-A(-/-)] and wild-type [SP-A(+/+)] mice. Concentrations of tumor necrosis factor (TNF);or, macrophage inflammatory protein-2, and nitric oxide were determined in recovered bronchoalveolar lavage fluid after intratracheal administration of LPS. SP-A(-/-) mice produced significantly more TNF-alpha and nitric oxide than SP-A(+/+) mice after LPS treatment. Intratracheal administration of human SP-A (1 mg/kg) to SP-A(-/-) mice restored regulation of TNF-alpha, macrophage inflammatory protein-2, and nitric oxide production to that of SP-A(+/+) mice, Other markers of lung injury including bronchoalveolar fluid protein, phospholipid content, and neutrophil numbers were not influenced by SP-A. Data from experiments designed to test possible mechanisms of SP-A-mediated suppression suggest that neither binding of LPS by SP-A nor enhanced LPS clearance are the primary means of inhibition. Our data and others suggest that SP-A acts directly on immune cells to suppress LPS-induced inflammation. These results demonstrate that endogenous or exogenous SP-A inhibits pulmonary LPS-induced cytokine and nitric oxide production in vivo.