Soderberg L S, Chang L W, Barnett J B
Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, USA.
J Leukoc Biol. 1996 Oct;60(4):459-64. doi: 10.1002/jlb.60.4.459.
Abuse of nitrite inhalants, widespread among male homosexuals, has been identified by epidemiological studies as an independent risk factor for AIDS and for Kaposi's sarcoma. Subchronic exposure of mice to inhaled isobutyl nitrite was previously found to impair the tumoricidal activity of peritoneal macrophages. Because inhalants would be expected to have the greatest effects on cells in the lung, alveolar macrophages from exposed mice were examined in this study. Mice were exposed to 900 ppm isobutyl nitrite in an inhalation chamber for 45 min/day for 14 days. Following this treatment, the lungs of exposed mice had large increases in cellularity, both in the alveolar septa and within the alveoli. Bronchoalveolar lavages also contained increased numbers of cells. Alveolar macrophages collected from treated mice had increased tumoricidal activity compared with controls and produced higher levels of inducible nitric oxide and tumor necrosis factor-alpha (TNF-alpha). The frequency of alveolar cells secreting TNF-alpha was increased ninefold in mice exposed to the inhalant. Cell influx into the lung, as indicated by the presence of red blood cells in lung lavages, was evident after only a single 45-min exposure to inhaled isobutyl nitrite at doses as low as 300 ppm.
流行病学研究已证实，亚硝酸盐吸入剂的滥用在男性同性恋者中广泛存在，是导致艾滋病和卡波西肉瘤的一个独立风险因素。此前发现，小鼠亚慢性吸入亚硝酸异丁酯会损害腹腔巨噬细胞的杀肿瘤活性。由于预计吸入剂对肺部细胞影响最大，因此本研究对暴露小鼠的肺泡巨噬细胞进行了检测。将小鼠置于吸入舱中，使其暴露于900 ppm亚硝酸异丁酯环境下，每天45分钟，持续14天。经过该处理后，暴露小鼠的肺部在肺泡隔和肺泡内的细胞数量大幅增加。支气管肺泡灌洗中的细胞数量也有所增加。与对照组相比，从处理过的小鼠收集的肺泡巨噬细胞具有更高的杀肿瘤活性，并产生更高水平的诱导型一氧化氮和肿瘤坏死因子-α（TNF-α）。暴露于吸入剂的小鼠中，分泌TNF-α的肺泡细胞频率增加了九倍。仅单次45分钟暴露于低至300 ppm的吸入亚硝酸异丁酯后，肺灌洗中出现红细胞表明有细胞流入肺部。
