FUNCTION OF IL8 AND NEUTROPHILS AFTER OZONE INJURY

臭氧是光化学烟雾的主要成分，也是世界上最重要的空气污染物之一。短期臭氧暴露会导致肺上皮细胞坏死，主要是I型细胞和中心细胞区的纤毛细胞。最近的实验研究表明，中性粒细胞的流入，进展到上皮损伤部位，有助于去除坏死的上皮细胞，加速上皮修复。暴露在臭氧中的呼吸道上皮细胞可上调IL-8的产生，但其与中性粒细胞流入相关的功能尚不清楚。中性粒细胞进入臭氧损伤区域并帮助清除臭氧损伤的呼吸道上皮细胞的机制尚不清楚。永生化原代人和恒河猴支气管上皮细胞体外臭氧暴露后，将研究下列特定目标：1)鉴定暴露于环境臭氧水平后产生IL-8的呼吸道上皮细胞(S)的表型；2)确定中性粒细胞是否直接迁移至臭氧损伤的呼吸道上皮细胞3)确定暴露于环境臭氧水平的呼吸道上皮细胞产生IL-8是否与中性粒细胞共存相关。

Ozone is a major component of photochemical smog and one of the most important air pollutants worldwide. Short-term ozone exposure causes epithelial necrosis in the lung, primarily of type I and ciliated cells in centriacinar regions. Recent experimental investigations have shown that the neutrophilic influx, which progresses to sites of epithelial injury, aids in the removal of necrotic epithelial cells and expedites epithelial repair. IL-8 production is upregulated by ozone exposed airway epithelium, but its' function relative to the neutrophil influx is not well defined. The mechanisms by which neutrophils traffic to an area of ozone injury and aid in the removal of ozone injured airway epithelial cells are unknown. After in vitro ozone exposure of immortalized and primary human and Rhesus monkey bronchial epithelial cells, the following specific aims will be investigated: 1) characterize the phenotype of the airway epithelial cell(s) that produce IL-8 after exposure to ambient levels of ozone 2) determine whether neutrophils migrate directly to ozone injured airway epithelial cells 3) determine if IL-8 production by airway epithelium exposed to ambient levels of ozone correlates with the co-localization of neutrophils.