Cho H Y, Hotchkiss J A, Bennett C B, Harkema J R
Departments of Pathology and Pharmacology, and Toxicology, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan, USA.
Am J Respir Crit Care Med. 2000 Aug;162(2 Pt 1):629-36. doi: 10.1164/ajrccm.162.2.9811078.
Ozone induces epithelial hyperplasia and mucous cell metaplasia (MCM) in nasal transitional epithelium (NTE) of rats. A transient neutrophil influx accompanies upregulation of mucin messenger RNA (mRNA) before the onset of MCM. The present study was designed to examine the role of neutrophils in ozone-induced epithelial changes in the NTE of rats. Fourteen hours before inhalation exposure, male F344/N rats were injected intraperitoneally with antirat neutrophil antiserum to deplete circulating neutrophils, or were injected with normal (control) serum. Rats were then exposed to 0 ppm (filtered air) or 0.5 ppm ozone (8 h/d) for 1 or 3 d. Maxilloturbinates lined with NTE were analyzed to determine the epithelial labeling index; numeric densities of neutrophils, total epithelial cells, and mucous secretory cells; amount of stored intraepithelial mucosubstances; and steady-state ratMUC-5AC (mucin) mRNA levels. At 2 h after 3 d of exposure, rats treated with antiserum had 90% fewer circulating neutrophils than did rats treated with control serum. Antiserum-treated, ozone-exposed rats had 87% fewer infiltrating neutrophils than did control serum-treated, ozone-exposed rats. At 4 d after 3 d of exposure, antiserum-treated, ozone-exposed rats had 66% less stored intraepithelial mucosubstances and 58% fewer mucous cells in their NTE than did control serum-treated, ozone-exposed rats. Antiserum treatment had no effects on ozone-induced epithelial cell proliferation or mucin mRNA upregulation. The results of this study indicated that ozone-induced MCM was neutrophil-dependent, whereas ozone-induced epithelial cell proliferation and mucin gene upregulation were neutrophil-independent.
臭氧可诱导大鼠鼻过渡上皮（NTE）发生上皮增生和黏液细胞化生（MCM）。在MCM发生之前，短暂的中性粒细胞浸润伴随着黏蛋白信使核糖核酸（mRNA）的上调。本研究旨在探讨中性粒细胞在臭氧诱导的大鼠NTE上皮变化中的作用。在吸入暴露前14小时，给雄性F344/N大鼠腹腔注射抗大鼠中性粒细胞抗血清以耗尽循环中的中性粒细胞，或注射正常（对照）血清。然后将大鼠暴露于0 ppm（过滤空气）或0.5 ppm臭氧（每天8小时）中1天或3天。分析内衬NTE的鼻鼻甲，以确定上皮标记指数；中性粒细胞、总上皮细胞和黏液分泌细胞的数值密度；上皮内储存的黏液物质的量；以及大鼠MUC-5AC（黏蛋白）mRNA的稳态水平。在暴露3天后的2小时，用抗血清处理的大鼠循环中性粒细胞比用对照血清处理的大鼠少90%。用抗血清处理、暴露于臭氧的大鼠浸润的中性粒细胞比用对照血清处理、暴露于臭氧的大鼠少87%。在暴露3天后的4天，用抗血清处理、暴露于臭氧的大鼠NTE中的上皮内储存黏液物质减少66%，黏液细胞减少58%。抗血清处理对臭氧诱导的上皮细胞增殖或黏蛋白mRNA上调没有影响。本研究结果表明，臭氧诱导的MCM依赖于中性粒细胞，而臭氧诱导的上皮细胞增殖和黏蛋白基因上调则不依赖于中性粒细胞。
