MCP-1/CCR2 signalling pathway regulates hyperoxia-induced acute lung injury via nitric oxide production
MCP-1/CCR2 signalling pathway regulates hyperoxia-induced acute lung injury via nitric oxide production
复制标题
DOI：
10.1111/j.1365-2613.2006.00502.x
复制
发表时间：
2006-12-01
影响因子：
3
通讯作者：
Takeya, Motohiro
中科院分区：
文献类型：
--
作者：
Okuma, Toshiyuki;Terasaki, Yasuhiro;Takeya, Motohiro
为了阐明单核细胞趋化蛋白 1 (MCP-1)/C-C 趋化因子受体 2 (CCR2) 信号通路在高氧诱导的急性肺损伤中的作用，将 CCR2 缺陷型 (CCR2-/-) 和野生型 (CCR2+/+) 小鼠暴露于 85% O-2 长达 6 天。第3天，与CCR2+/+小鼠相比，CCR2-/-小鼠的体重显着下降，支气管肺泡灌洗液（BALF）中的总蛋白浓度更高。 CCR2-/- 小鼠的累积存活率显着低于 CCR2+/+ 小鼠。然而，两组的组织学变化和BALF中巨噬细胞的数量没有显着差异。实时逆转录聚合酶链反应显示，与 CCR2+/+ 小鼠相比，CCR2-/- 小鼠肺组织中 MCP-1、白介素-1 β 硫氧还蛋白-1 和诱导型一氧化氮合酶 (iNOS) 的 mRNA 水平升高。 CCR2-/- 小鼠体内或体外暴露于 85% O-2 48 小时的肺泡巨噬细胞中 iNOS mRNA 水平的增加显着高于 CCR2+/+ 小鼠。这些结果表明，MCP-1/CCR2 信号通路通过抑制 iNOS 的诱导以及随后活化的肺泡巨噬细胞产生活性氧，从而防止高氧诱导的组织损伤。
To clarify the role of the monocyte chemoattractant protein-1 (MCP-1)/C-C chemokine receptor 2 (CCR2) signalling pathway in hyperoxia-induced acute lung injury, CCR2-deficient (CCR2-/-) and wild-type (CCR2+/+) mice were exposed to 85% O-2 for up to 6 days. At day 3, body weight significantly decreased and total protein concentration in bronchoalveolar lavage fluid (BALF) was higher in CCR2-/- mice compared with CCR2+/+ mice. Cumulative survivals were significantly lower in CCR2-/- mice than in CCR2+/+ mice. However, the two groups showed no significant differences in both histological changes and number of macrophages in BALF. Real-time reverse transcriptase-polymerase chain reaction revealed increased mRNA levels of MCP-1, interleukin-1 beta thioredoxin-1, and inducible nitric oxide synthase (iNOS) in lung tissues in CCR2-/- mice compared with CCR2+/+ mice. Increased iNOS mRNA levels in alveolar macrophages exposed to 85% O-2 for 48 h in vivo or in vitro were significantly higher in CCR2-/- mice than in CCR2+/+ mice. These results suggest that the MCP-1/CCR2 signalling pathway is protective against hyperoxia-induced tissue injury by suppressing induction of iNOS and consequent production of reactive oxygen species by activated alveolar macrophages.