Esterline R L, Bassett D J, Trush M A
Department of Environmental Health Sciences, Johns Hopkins University School of Hygiene and Public Health, Baltimore, Maryland 21205.
Toxicol Appl Pharmacol. 1989 Jun 15;99(2):229-39. doi: 10.1016/0041-008x(89)90005-7.
Following exposure to 2 ppm ozone for 4 hr, two distinct effects on rat lung inflammatory cell oxidant generation were observed. TPA- and opsonized zymosan-stimulated superoxide production by the inflammatory cell population was found to be maximally inhibited 24 hr following ozone exposure. In contrast, luminol-amplified chemiluminescence increased 24 hr following ozone exposure, coinciding with an increase in the percentage of neutrophils and myeloperoxidase in the inflammatory cell population. Supporting the involvement of myeloperoxidase in the enhanced oxidant-generating status of these cells, the luminol-amplified chemiluminescence was found to be azide-, but not superoxide dismutase-inhibitable. Additionally, this cell population was found to generate taurine chloramines, a myeloperoxidase-dependent function which was absent prior to the ozone exposure and also demonstrated enhanced activation of benzo[a]pyrene-7,8-dihydrodiol to its light-emitting dioxetane intermediate. Addition of myeloperoxidase to control alveolar macrophages resulted in enhanced luminol-amplified chemiluminescence, taurine chloramine generation, and enhanced chemiluminescence from benzo[a]pyrene-7,8-dihydrodiol demonstrating that, in the presence of myeloperoxidase, alveolar macrophages are capable of supporting myeloperoxidase-dependent reactions. The possibility of such an interaction occurring in vivo is suggested by the detection of myeloperoxidase activity in the cell-free lavagates of ozone-exposed rats. These studies suggest that neutrophils recruited to ozone-exposed lungs alter the oxidant-generating capabilities in the lung which could further contribute to lung injury or to the metabolism of inhaled xenobiotics.
在大鼠暴露于2 ppm臭氧4小时后，观察到对大鼠肺部炎症细胞氧化剂生成有两种不同的影响。发现暴露于臭氧后24小时，炎症细胞群体经佛波酯（TPA）和调理酵母聚糖刺激的超氧化物生成受到最大程度的抑制。相比之下，暴露于臭氧后24小时，鲁米诺增强化学发光增加，这与炎症细胞群体中中性粒细胞百分比和髓过氧化物酶的增加相一致。支持髓过氧化物酶参与这些细胞氧化剂生成增强状态的证据是，发现鲁米诺增强化学发光可被叠氮化物抑制，但不能被超氧化物歧化酶抑制。此外，还发现该细胞群体可生成牛磺酸氯胺，这是一种依赖髓过氧化物酶的功能，在臭氧暴露前不存在，并且还显示苯并[a]芘-7,8-二氢二醇向其发光二氧杂环丁烷中间体的活化增强。向对照肺泡巨噬细胞中添加髓过氧化物酶导致鲁米诺增强化学发光、牛磺酸氯胺生成增加以及苯并[a]芘-7,8-二氢二醇化学发光增强，这表明在髓过氧化物酶存在的情况下，肺泡巨噬细胞能够支持依赖髓过氧化物酶的反应。在暴露于臭氧的大鼠无细胞灌洗液中检测到髓过氧化物酶活性，提示了体内发生这种相互作用的可能性。这些研究表明，招募到暴露于臭氧的肺部的中性粒细胞会改变肺部的氧化剂生成能力，这可能进一步导致肺损伤或吸入异源生物物质的代谢。
