Harkema J R, Hotchkiss J A
Inhalation Toxicology Research Institute, Albuquerque, New Mexico 87185.
Exp Lung Res. 1991 Jul-Aug;17(4):743-61. doi: 10.3109/01902149109062876.
Airway inflammation induced by gram-negative bacteria is often characterized by an influx of neutrophils and hypersecretion of mucus. The purpose of this study was to determine how endotoxin, a component of gram-negative bacteria and a chemotaxinogen for neutrophils, affects the amount of stored intraepithelial mucosubstances in the rat nasal airway. Rats were intranasally instilled, once a day for 3 days, with endotoxin or saline (controls). Before the first and third instillation, half of the animals were depleted of circulating blood neutrophils by administering a rabbit anti-rat neutrophil antiserum. Rats were sacrificed 6 or 24 h after the last instillation. Nasal tissues were processed for light microscopy and histochemical detection of stored intraepithelial mucosubstances. The numbers of nasal epithelial cells and intraepithelial neutrophils per millimeter of basal lamina in the anterior nasal septum and the amounts of intraepithelial mucosubstances in the same nasal tissue were determined by image analysis. We did not observe a neutrophil influx in the nasal tissues of neutrophil-depleted rats at 6 or 24 h after the last endotoxin instillation; however, we did observe a significant increase in intraepithelial mucosubstances, compared to saline-instilled controls. In contrast, nonneutrophil-depleted animals had a marked neutrophilic influx and a concomitant decrease in stored mucosubstances, compared to saline-instilled controls. There was no significant difference in the number of nasal epithelial cells per millimeter of basal lamina among any of the experimental groups. These results indicate (1) that endotoxin induces an increase in the amount of intraepithelial mucosubstances only when intraepithelial neutrophils are absent, and (2) that the endotoxin-induced, neutrophil influx probably triggers mucous hypersecretion.
革兰氏阴性菌引起的气道炎症通常表现为中性粒细胞浸润和黏液分泌过多。本研究的目的是确定内毒素（革兰氏阴性菌的一种成分，也是中性粒细胞的趋化因子）如何影响大鼠鼻气道中上皮内储存的黏液物质的量。大鼠每天经鼻内滴注一次，连续3天，分别滴注内毒素或生理盐水（对照组）。在第一次和第三次滴注前，通过给予兔抗大鼠中性粒细胞抗血清，使一半动物的循环血中性粒细胞减少。在最后一次滴注后6或24小时处死大鼠。对鼻组织进行处理，用于光学显微镜检查和上皮内储存的黏液物质的组织化学检测。通过图像分析确定前鼻中隔每毫米基膜的鼻上皮细胞和上皮内中性粒细胞数量，以及同一鼻组织中的上皮内黏液物质含量。在最后一次内毒素滴注后6或24小时，我们未在中性粒细胞减少的大鼠鼻组织中观察到中性粒细胞浸润；然而，与滴注生理盐水的对照组相比，我们确实观察到上皮内黏液物质显著增加。相比之下，与滴注生理盐水的对照组相比，未减少中性粒细胞的动物有明显的中性粒细胞浸润，同时储存的黏液物质减少。任何实验组每毫米基膜的鼻上皮细胞数量均无显著差异。这些结果表明：（1）仅当上皮内不存在中性粒细胞时，内毒素才会诱导上皮内黏液物质的量增加；（2）内毒素诱导的中性粒细胞浸润可能触发黏液分泌过多。
