Sone S, Brennan L M, Creasia D A
J Toxicol Environ Health. 1983 Jan;11(1):151-63. doi: 10.1080/15287398309530329.
Rat alveolar macrophages (AM) were exposed in vivo or in vitro to nitrogen dioxide (NO2) and subsequently tested for phagocytic and tumoricidal activities. AM obtained by lavage from Fischer 344/N rats exposed for 4 h to 40 ppm NO2 were significantly more phagocytic to opsonized sheep red blood cells (SRBC), exhibited an increased cytotoxic response toward syngeneic mammary adenocarcinoma cells, and were more sensitive to activation by agents such as lipopolysaccharide, muramyl dipeptide, and macrophage-activating factor, as compared with the response of AM obtained from unexposed control rats. Repeated 4 h/d NO2 exposures over 7-d or 14-d periods usually resulted in AM activity similar to control levels, with some instances of increased phagocytic activity of the AM but not to the extent of that observed for a single 4 h exposure. There were no significant decreases in the cytotoxic or phagocytic activities of the AM during any of the exposure periods. For the in vitro exposures, AM were lavaged from normal rats and then exposed for various periods to 10, 20, or 40 ppm NO2. A dose-related and time-dependent enhanced cytotoxic response of AM was observed. Maximum AM-mediated cytotoxicity occurred after an in vitro exposure to 10 ppm NO2 for 2 h. The cytotoxic response was directed toward syngeneic mammary adenocarcinoma cells but not against syngeneic embryoblast cells, indicating that the AM retained the ability to distinguish between normal and abnormal cells. No inhibitory effects of NO2 on AM-mediated cytotoxicity were observed. These experiments suggest that the host AM-mediated immune defense of the lung may be modulated by host exposure to inhaled chemicals.
将大鼠肺泡巨噬细胞（AM）在体内或体外暴露于二氧化氮（NO₂），随后检测其吞噬和杀肿瘤活性。通过灌洗从暴露于40 ppm NO₂ 4小时的Fischer 344/N大鼠获得的AM，对调理过的绵羊红细胞（SRBC）的吞噬能力显著增强，对同基因乳腺腺癌细胞的细胞毒性反应增强，并且与从未暴露的对照大鼠获得的AM相比，对脂多糖、胞壁酰二肽和巨噬细胞激活因子等试剂的激活更敏感。在7天或14天内每天重复4小时的NO₂暴露，通常会使AM活性恢复到对照水平，在某些情况下，AM的吞噬活性会增加，但增加程度不及单次4小时暴露时观察到的程度。在任何暴露期间，AM的细胞毒性或吞噬活性均无显著降低。对于体外暴露，从正常大鼠中灌洗出AM，然后将其暴露于10、20或40 ppm NO₂ 不同时间段。观察到AM的细胞毒性反应呈剂量相关和时间依赖性增强。在体外暴露于10 ppm NO₂ 2小时后，AM介导的细胞毒性达到最大值。细胞毒性反应针对同基因乳腺腺癌细胞，而不针对同基因胚胎细胞，这表明AM保留了区分正常细胞和异常细胞的能力。未观察到NO₂对AM介导的细胞毒性有抑制作用。这些实验表明，宿主暴露于吸入性化学物质可能会调节宿主AM介导的肺部免疫防御。
