Koike E, Kobayashi T, Utsunomiya R
Department of Medicine, Tsukuba University, 305-8575, Tsukuba, Japan.
Toxicol Lett. 2001 Apr 30;121(2):135-43. doi: 10.1016/s0378-4274(01)00331-9.
Nitrogen dioxide (NO2), a major component of air pollutants, induces inflammatory responses in the lungs. Resident alveolar macrophages (AM) play an immunosuppressive role in the lungs via suppression of lymphocyte proliferation, and nitric oxide (NO) plays a crucial role in this immunosuppressive activity. Microenvironmental changes within the alveoli during inflammatory responses, however, can inhibit this immunosuppressive activity of AM. The present study was designed to clarify the effect of NO2 exposure on the immunosuppressive activity of and NO production by AM in rats. Wistar rats were exposed to 10 ppm NO2 for 3, 14 or 28 days, after which bronchoalveolar lavage fluid (BALF) was taken as a sample of the alveolar microenvironment. Suppression of concanavalin A-induced lymphocyte proliferation and NO production by AM were markedly inhibited by BALF from NO2-exposed rats (NO2-BALF). The inhibitory effect of NO2-BALF at 28-days exposure was stronger than that of NO2-BALF at 3 or 14 days exposure. In conclusion, AM-mediated immunosuppressive activity was inhibited by the NO2-induced changes of the alveolar microenvironment through the inhibition of NO production.
二氧化氮（NO₂）是空气污染物的主要成分，可诱发肺部炎症反应。驻留肺泡巨噬细胞（AM）通过抑制淋巴细胞增殖在肺部发挥免疫抑制作用，一氧化氮（NO）在这种免疫抑制活性中起关键作用。然而，炎症反应期间肺泡内的微环境变化可抑制AM的这种免疫抑制活性。本研究旨在阐明暴露于NO₂对大鼠AM免疫抑制活性及NO产生的影响。将Wistar大鼠暴露于10 ppm NO₂中3天、14天或28天，之后采集支气管肺泡灌洗液（BALF）作为肺泡微环境的样本。来自暴露于NO₂的大鼠的BALF（NO₂-BALF）显著抑制了AM对伴刀豆球蛋白A诱导的淋巴细胞增殖的抑制作用及NO的产生。暴露28天的NO₂-BALF的抑制作用强于暴露3天或14天的NO₂-BALF。总之，NO₂诱导的肺泡微环境变化通过抑制NO产生抑制了AM介导的免疫抑制活性。
