Zhao Q, Simpson L G, Driscoll K E, Leikauf G D
Department of Environmental Health, University of Cincinnati 45267, USA.
Am J Physiol. 1998 Jan;274(1):L39-46. doi: 10.1152/ajplung.1998.274.1.L39.
Pulmonary inflammation has been observed in humans and in many animal species after ozone exposure. Inflammatory cell accumulation involves local synthesis of chemokines, including neutrophil chemoattractants such as macrophage inflammatory protein-2 (MIP-2), and monocyte chemoattractants, such as monocyte chemoattractant protein-1 (MCP-1). To better understand the mechanism of ozone-induced inflammation, we exposed mice and rats to ozone for 3 h and measured MIP-2 and MCP-1 gene expression. In C57BL/6 mice, steady-state mRNA levels for MCP-1 in the lung increased at 0.6 parts/million (ppm) ozone and were maximal at 2.0 ppm ozone. After exposure to 2 ppm ozone, MIP-2 mRNA levels peaked at 4 h postexposure, whereas MCP-1 mRNA levels peaked at 24 h postexposure. Neutrophils and monocytes recovered in bronchoalveolar lavage fluid peaked at 24 and 72 h, respectively. The accumulation of monocytes was thus delayed relative to that of neutrophils, consistent with the sequential expression of the corresponding chemokines. The role of MCP-1 in monocyte accumulation was evaluated in greater detail in rats. Ozone caused an increase in monocyte chemotactic activity in bronchoalveolar fluid that was inhibited by an antibody directed against MCP-1. Ozone-induced MCP-1 mRNA levels were higher in lavage cells than in whole lung tissue, indicating that lavage cells are an important source of MCP-1. In these cells, nuclear factor-kappa B, a nuclear transcription factor implicated in MCP-1 gene regulation, was also activated 20-24 h after ozone exposure. These findings indicate that monocyte accumulation subsequent to acute lung injury can be mediated through MCP-1 and that nuclear factor-kappa B may play a role in ozone-induced MCP-1 gene expression.
在人类和许多动物物种中，臭氧暴露后均可观察到肺部炎症。炎症细胞的聚集涉及趋化因子的局部合成，包括中性粒细胞趋化因子，如巨噬细胞炎性蛋白-2（MIP-2），以及单核细胞趋化因子，如单核细胞趋化蛋白-1（MCP-1）。为了更好地理解臭氧诱导炎症的机制，我们将小鼠和大鼠暴露于臭氧中3小时，并测量MIP-2和MCP-1基因的表达。在C57BL/6小鼠中，肺中MCP-1的稳态mRNA水平在臭氧浓度为0.6百万分率（ppm）时升高，并在2.0 ppm臭氧时达到最大值。暴露于2 ppm臭氧后，MIP-2 mRNA水平在暴露后4小时达到峰值，而MCP-1 mRNA水平在暴露后24小时达到峰值。支气管肺泡灌洗液中回收的中性粒细胞和单核细胞分别在24小时和72小时达到峰值。因此，单核细胞的聚集相对于中性粒细胞有所延迟，这与相应趋化因子的顺序表达一致。在大鼠中更详细地评估了MCP-1在单核细胞聚集中的作用。臭氧导致支气管肺泡液中单核细胞趋化活性增加，而针对MCP-1的抗体可抑制这种活性。臭氧诱导的MCP-1 mRNA水平在灌洗细胞中高于全肺组织，表明灌洗细胞是MCP-1的重要来源。在这些细胞中，参与MCP-1基因调控的核转录因子核因子-κB在臭氧暴露后20 - 24小时也被激活。这些发现表明，急性肺损伤后单核细胞的聚集可通过MCP-1介导，并且核因子-κB可能在臭氧诱导的MCP-1基因表达中发挥作用。
