Effect of CD14 blockade on endotoxin-induced acute lung injury in mice
Effect of CD14 blockade on endotoxin-induced acute lung injury in mice
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DOI：
10.1165/rcmb.2002-0132oc
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发表时间：
2003-08-01
影响因子：
6.4
通讯作者：
Yamaguchi, K
中科院分区：
文献类型：
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作者：
Tasaka, S;Ishizaka, A;Yamaguchi, K
CD 14作为内毒素（脂多糖[LPS]）的细胞表面受体发挥作用，并被认为在对感染的先天免疫应答中起重要作用。先前的研究已经揭示了通过阻断CD 14来减弱脓毒症后的全身反应。在这项研究中，我们测试了CD 14阻断剂保护与LPS肺炎相关的炎症反应的假设。我们研究了抗鼠CD 14单克隆抗体（4C 1）对小鼠内毒素诱导的急性肺损伤的影响。我们还测量了细胞因子（肿瘤坏死因子-α，白细胞介素-6，巨噬细胞炎性蛋白-2）和一氧化氮的小鼠腹腔巨噬细胞暴露于LPS在体外的生产。在肺匀浆的核提取物中评价核因子（NF）-κ B易位。4C 1显著减弱LPS施用后的肺水肿和中性粒细胞移出。4C 1处理显著降低了LPS刺激的巨噬细胞的细胞因子和一氧化氮的产生。4C 1还抑制LPS滴注诱导的NF-κ B易位。这些结果表明，阻断CD 14可能通过抑制NF-κ B易位减轻LPS肺内滴注后的急性肺损伤。阻断CD 14对巨噬细胞产生细胞因子和释放一氧化氮的抑制作用可能是减轻肺损伤的机制之一。
CD14 functions as a cell surface receptor for endotoxin (lipopolysaccharide [LPS]) and is thought to have an essential role in innate immune responses to infection. Previous studies have revealed attenuation of the systemic response after sepsis by blocking CD14. In this study, we tested the hypothesis that CD14 blockade protects against inflammatory responses associated with LPS pneumonia. We examined the effect of an anti-murine CD14 monoclonal antibody (4C1) on the development of acute lung injury induced by intratracheal LPS in mice. We also measured the production of cytokines (tumor necrosis factor-alpha, interleukin-6, and macrophage inflammatory protein-2) and nitric oxide by murine peritoneal macrophages exposed to LPS in vitro. Nuclear factor (NF)-KB translocation was evaluated in nuclear extracts from lung homogenates. 4C1 significantly attenuated pulmonary edema and neutrophil emigration after LPS administration. The production of cytokines and nitric oxide by LPS-stimulated macrophages was significantly decreased by 4C1 treatment. NF-KB translocation induced by LPS instillation was also suppressed by 4C1. These results suggest that blockade of CD14 might attenuate acute lung injury after intratracheal instillation of LPS through the suppression of NF-KB translocation. The inhibitory effect of CD14 blockade on cytokine production and nitric oxide release of macrophages might contribute to the attenuation of lung injury.