Kleinerman J, Ip M P, Sorensen J
Am Rev Respir Dis. 1982 Feb;125(2):203-7. doi: 10.1164/arrd.1982.125.2.203.
Adult male hamsters were exposed to 30 +/- 5 ppm nitrogen dioxide (NO2) for periods as long as 30 days. Alveolar macrophages obtained by lung lavage at 0, 2, 5, 14, and 30 days of exposure were present in increased amounts, with the greatest increase 8 times the control amount at 14 days of NO2 exposure. No elastolytic activity was observed in the cell-free lavage fluid. Alveolar macrophages were cultured in serum-free medium for 1 to 6 days. The mediums were collected and assayed for elastolytic activity using Sepharose-coupled [3H] soluble elastin as substrate. Elastolytic activity in the secretions increased significantly at days 2 and 5 but was greatest after 14 days of NO2 exposure. These observations indicate that the secretions of alveolar macrophages from hamsters exposed to NO2 increased elastolytic activity. This activity correlates with the duration of NO2 exposure for periods as long as 14 days. The increased elastolysis observed appears to be dependent on increased numbers of macrophages rather than on increased elastolytic secretion per cell. Inhibition studies with a battery of elastase inhibitors indicated that the elastase(s) secreted from NO2 and control alveolar macrophages have identical properties. The response of hamster macrophage elastase to inhibitors differs from that observed in the mouse and in humans in that it is not inhibited by EDTA, human serum or 1,10-phenanthroline.
成年雄性仓鼠暴露于30±5 ppm的二氧化氮(NO₂)中长达30天。在暴露的第0、2、5、14和30天通过肺灌洗获得的肺泡巨噬细胞数量增加,在NO₂暴露14天时增加最多,是对照数量的8倍。在无细胞灌洗液中未观察到弹性蛋白酶活性。肺泡巨噬细胞在无血清培养基中培养1至6天。收集培养基并使用琼脂糖偶联的[³H]可溶性弹性蛋白作为底物测定弹性蛋白酶活性。分泌物中的弹性蛋白酶活性在第2天和第5天显著增加,但在NO₂暴露14天后最高。这些观察结果表明,暴露于NO₂的仓鼠肺泡巨噬细胞分泌物增加了弹性蛋白酶活性。这种活性与长达14天的NO₂暴露持续时间相关。观察到的弹性蛋白酶增加似乎取决于巨噬细胞数量的增加,而不是每个细胞弹性蛋白酶分泌的增加。用一系列弹性蛋白酶抑制剂进行的抑制研究表明,从NO₂和对照肺泡巨噬细胞分泌的弹性蛋白酶具有相同的特性。仓鼠巨噬细胞弹性蛋白酶对抑制剂的反应与在小鼠和人类中观察到的不同,因为它不受EDTA、人血清或1,10-菲咯啉的抑制。