Koike E, Kobayashi T, Nelson D J, McWilliam A S, Holt P G
Department of Medical Sciences, Tsukuba University, Tsukuba, 305, Japan.
Toxicol Sci. 1998 Feb;41(2):217-23. doi: 10.1006/toxs.1997.2417.
Ozone (O3), a major component of photochemical air pollution, is a strong oxidizing agent and highly toxic. Resident alveolar macrophages (AM) play an important immunomodulatory role in the lung via suppression of lymphocyte proliferation, thus limiting the magnitude and duration of local immune responses. Nitric oxide (NO) plays a crucial role in the immunosuppressive activity of AM. However, during immunoinflammatory responses, microenvironmental changes within the alveoli inhibit this AM function, permitting full expression of local T-cell-mediated immune responses. We hypothesize that similar changes in AM function may occur during inflammation induced by exposure to inorganic air pollutants, such as O3. In order to test this hypothesis, in the present study, we investigated (1) whether O3 exposure of rats might affect the immunosuppressive activity and NO production of bronchoalveolar lavage cells (BAL cells) and (2) whether changes in the microenvironment of the alveoli induced by O3 exposure can affect the immunosuppressive activity and NO production of AM. AM-mediated immunosuppressive activity was measured as inhibition of concanavalin A (Con A)-induced proliferation of lymph node cells (LNC). Bronchoalveolar lavage was used to sample the alveolar microenvironment, and the resulting fluid (BALF) was tested for capacity to modulate AM activity in the cultures. BALF and BAL cells from rats exposed to 1 ppm O3 or filtered air for 3 days were used. The present results demonstrate that BAL cells isolated from O3-exposed rats suppressed Con A-induced LNC proliferation and produced NO in the same manner as BAL cells (AM) from air-exposed rats. AM-mediated suppressive activity of LNC proliferation and NO production were markedly inhibited by BALF from O3-exposed but not from air-exposed rats. These results suggested that AM-mediated immunosuppressive activity in vivo may be inhibited by the O3-induced release of soluble factors which inhibit NO production by AM.
臭氧（O₃）是光化学空气污染的主要成分，是一种强氧化剂且毒性很高。驻留肺泡巨噬细胞（AM）通过抑制淋巴细胞增殖在肺部发挥重要的免疫调节作用，从而限制局部免疫反应的强度和持续时间。一氧化氮（NO）在AM的免疫抑制活性中起关键作用。然而，在免疫炎症反应期间，肺泡内的微环境变化会抑制这种AM功能，使局部T细胞介导的免疫反应得以充分表达。我们推测，在暴露于无机空气污染物（如O₃）引起的炎症过程中，AM功能可能会发生类似变化。为了验证这一假设，在本研究中，我们调查了：（1）大鼠暴露于O₃是否会影响支气管肺泡灌洗细胞（BAL细胞）的免疫抑制活性和NO生成；（2）O₃暴露引起的肺泡微环境变化是否会影响AM的免疫抑制活性和NO生成。以抑制伴刀豆球蛋白A（Con A）诱导的淋巴结细胞（LNC）增殖来衡量AM介导的免疫抑制活性。采用支气管肺泡灌洗来采集肺泡微环境样本，并检测所得液体（BALF）在培养物中调节AM活性的能力。使用暴露于1 ppm O₃或过滤空气3天的大鼠的BALF和BAL细胞。目前的结果表明，从暴露于O₃的大鼠中分离出的BAL细胞抑制Con A诱导的LNC增殖，并以与暴露于空气的大鼠的BAL细胞（AM）相同的方式产生NO。暴露于O₃而非暴露于空气的大鼠的BALF显著抑制了AM介导的LNC增殖抑制活性和NO生成。这些结果表明，体内AM介导的免疫抑制活性可能会被O₃诱导释放的可溶性因子所抑制，这些因子会抑制AM产生NO。
