Diesel exhaust particles enhance lung injury related to bacterial endotoxin through expression of proinflammatory cytokines, chemokines, and intercellular adhesion molecule-1
Diesel exhaust particles enhance lung injury related to bacterial endotoxin through expression of proinflammatory cytokines, chemokines, and intercellular adhesion molecule-1
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DOI：
10.1164/rccm.2108122
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发表时间：
2002-05-01
影响因子：
24.7
通讯作者：
Morita, M
中科院分区：
文献类型：
--
作者：
Takano, H;Yanagisawa, R;Morita, M
流行病学研究表明，空气微粒污染对呼吸系统健康产生急性和严重的不利影响，特别是对易受细菌感染的人。然而，潜在的机制仍有待阐明。为了给流行病学数据提供实验依据，我们测定了颗粒污染物的主要参与者柴油机尾气颗粒（DEP）对细菌内毒素引起的小鼠肺损伤的影响。气管内滴注DEPs可协同增强革兰氏阴性菌内毒素相关的肺损伤，其特征为中性粒细胞隔离、间质水肿和肺泡出血。在内毒素存在下，DEPs进一步激活肺内核因子- κ b (nf - κ b) p65亚基的核易位，增加肺内细胞间粘附分子-1、白细胞介素-1 β、巨噬细胞趋化蛋白-1、角化细胞趋化蛋白（KC）、巨噬细胞炎症蛋白-1 α和toll样受体的表达。单独给药DEPs增加了肺部toll样受体4的表达和NF-kappaB p50亚基的核定位。DEPs和内毒素联合暴露降低了CCAAT/增强子结合蛋白β的核定位。这些结果提供了DEPs增强与细菌内毒素相关的中性粒细胞肺炎症的第一个实验证据。这种增强是由促炎分子的诱导介导的，可能是通过toll样受体的表达和NF-kappaB含有p65的二聚体(s)的激活，如p65/p50。
Epidemiologic studies demonstrate acute and serious adverse effects of particulate air pollution on respiratory health, especially in people who are susceptible to bacterial infection. However, the underlying mechanism remains to be elucidated. To provide experimental evidence for the epidemiologic data, we determined the effects of diesel exhaust particles (DEP), major participants in particulate pollutants, on lung injury related to bacterial endotoxin in mice. Intratracheal instillation of DEPs synergistically enhanced lung injury related to endotoxin from gram-negative bacteria, which was characterized by neutrophil sequestration, interstitial edema, and alveolar hemorrhage. In the presence of endotoxin, DEPs further activated the nuclear translocation of p65 subunit of nuclear factor-kappaB (NF-kappaB) in the lung and increased the lung expression of intercellular adhesion molecule-1, interleukin-1beta, macrophage chemoattractant protein-1, keratinocyte chemoattractant (KC), macrophage inflammatory protein-1alpha, and Toll-like receptors. DEPs given alone increased the lung expression of Toll-like receptor 4 and the nuclear localization of p50 subunit of NF-kappaB. The combined exposure to DEPs and endotoxin decreased nuclear localization of CCAAT/enhancer binding protein beta. These results provide the first experimental evidence that DEPs enhance neutrophilic lung inflammation related to bacterial endotoxin. The enhancement is mediated by the induction of proinflammatory molecules, likely through the expression of Toll-like receptors and the activation of p65-containing dimer(s) of NF-kappaB, such as p65/p50.