Immunomodulating effects of ozone on macrophage functions important for tumor surveillance and host defense.
Immunomodulating effects of ozone on macrophage functions important for tumor surveillance and host defense.
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臭氧对巨噬细胞功能的免疫调节作用对于肿瘤监测和宿主防御很重要。
DOI：
10.1080/15287399109531582
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发表时间：
1991
期刊：
影响因子：
--
通讯作者：
Schlesinger,RB
中科院分区：
文献类型：
--
作者：
Zelikoff,JT;Kraemer,GL;Vogel,MC;Schlesinger,RB
臭氧（O3）是一种有毒的气态污染物，在实验室研究中被认为是小鼠的潜在肺癌致癌物或共致癌物。为了开始评估改变的巨噬细胞（M β）反应作为O3可能影响致癌作用的可能机制的作用，我们研究了重复体内O3暴露对肺M β功能和生化活动的影响，这些活动在肿瘤监测和宿主防御中被认为是重要的。将家兔吸入1 ppm O3，连续暴露3d（2 h/d），暴露后立即（t0）和24 h（t24）进行肺灌洗。结果表明，O3降低了M β的活力，增加了暴露后立即收集的中性粒细胞的数量。O3对M_（12）运动的影响表现为：末次暴露后M_（12）的随机运动立即受到抑制，24 h后M_（12）的趋化运动增强。与对照组相比，在O3暴露后即刻和24 h，M β介导的体外对异种肿瘤细胞的细胞毒性显著降低。还评估了被认为对介导肿瘤细胞破坏重要的细胞毒性因子的释放。通过对L-M细胞（L-929小鼠成纤维细胞的克隆）的细胞毒性测量，肿瘤坏死因子的自发和刺激产生不受O3暴露的影响。酵母多糖刺激的超氧阴离子自由基（·O−2）的产生在t0时被抑制，在t24时增加;然而，在任何时间间隔，都没有观察到静息或酵母多糖刺激的M β对H2 O2产生的显著影响。吸入有毒物质，如O3，可以损害肿瘤监测中重要的M β功能，可能会改变宿主对肺癌的易感性。这项研究的结果对人类健康具有重要意义，并表明需要进一步研究O3的致癌/致癌潜力。
Ozone (O3) is a toxic gaseous pollutant that has been implicated in laboratory studies as a potential lung carcinogen or cocarcinogen in mice. To begin to assess the role of altered macrophage (M⊘) responses as a possible mechanism by which O3may influence carcinogenesis, we examined the effects of repeated in vivo O3exposure on pulmonary M⊘ functional and biochemical activities deemed important in tumor surveillance, and host defense in general. Rabbits were exposed by inhalation to 1 ppm O3for 3 d (2 h/d) and the lungs were lavaged immediately (t0) and 24 h (t24) after exposure. Results demonstrate that O3reduced M⊘ viability and increased the number of neutrophils collected immediately after exposure. Effects of O3on M⊘ movement were as follows: random migration was depressed immediately after the final exposure and chemotactic migration increased after 24 h. M⊘‐mediated cytotoxicity toward xenogeneic tumor cells in vitro was significantly depressed, compared to control, immediately and 24 h after O3exposure. Release of cytotoxic factors deemed important for mediating tumor cell destruction was also assessed. Spontaneous and stimulated production of tumor necrosis factor, as measured by cytotoxicity toward L‐M cells (a clone of L‐929 mouse fibrobtasts), was unaffected by exposure to O3. Zymosan‐stimulated production of superoxide anion radical (·O−2) was depressed at t0and increased at t24; however, no significant effects on H2O2production by resting or zymosan‐stimulated M⊘ were observed at either time interval. Inhaled toxicants such as O3, which can compromise M⊘ functions important in tumor surveillance, could potentially alter host susceptibility to pulmonary cancer. Results of this study have important implications for human health, and demonstrate the need for further studies examining the carcinogenic/cocarcinogenic potential of O3.