Bouthillier L, Vincent R, Goegan P, Adamson I Y, Bjarnason S, Stewart M, Guénette J, Potvin M, Kumarathasan P
Environmental and Occupational Toxicology Division, Environmental Health Directorate, Health Canada, Ottawa, Ontario.
Am J Pathol. 1998 Dec;153(6):1873-84. doi: 10.1016/S0002-9440(10)65701-X.
We studied acute responses of rat lungs to inhalation of urban particulate matter and ozone. Exposure to particles (40 mg/m3 for 4 hours; mass median aerodynamic diameter, 4 to 5 microm; Ottawa urban dust, EHC-93), followed by 20 hours in clean air, did not result in acute lung injury. Nevertheless, inhalation of particles resulted in decreased production of nitric oxide (nitrite) and elevated secretion of macrophage inflammatory protein-2 from lung lavage cells. Inhalation of ozone (0.8 parts per million for 4 hours) resulted in increased neutrophils and protein in lung lavage fluid. Ozone alone also decreased phagocytosis and nitric oxide production and stimulated endothelin-1 secretion by lung lavage cells but did not modify secretion of macrophage inflammatory protein-2. Co-exposure to particles potentiated the ozone-induced septal cellularity in the central acinus but without measurable exacerbation of the ozone-related alveolar neutrophilia and permeability to protein detected by lung lavage. The enhanced septal thickening was associated with elevated production of both macrophage inflammatory protein-2 and endothelin-1 by lung lavage cells. Interestingly, inhalation of urban particulate matter increased the plasma levels of endothelin-1, but this response was not influenced by the synergistic effects of ozone and particles on centriacinar septal tissue changes. This suggests an impact of the distally distributed particulate dose on capillary endothelial production or filtration of the vasoconstrictor. Overall, equivalent patterns of effects were observed after a single exposure or three consecutive daily exposures to the pollutants. The experimental data are consistent with epidemiological evidence for acute pulmonary effects of ozone and respirable particulate matter and suggest a possible mechanism whereby cardiovascular effects may be induced by particle exposure. In a broad sense, acute biological effects of respirable particulate matter from ambient air appear related to paracrine/endocrine disruption mechanisms.
我们研究了大鼠肺部对吸入城市颗粒物和臭氧的急性反应。暴露于颗粒物（40毫克/立方米，持续4小时；质量中值空气动力学直径为4至5微米；渥太华城市灰尘，EHC - 93），随后在清洁空气中暴露20小时，并未导致急性肺损伤。然而，吸入颗粒物导致一氧化氮（亚硝酸盐）生成减少，肺灌洗细胞中巨噬细胞炎性蛋白 - 2的分泌增加。吸入臭氧（百万分之0.8，持续4小时）导致肺灌洗液中中性粒细胞和蛋白质增加。单独吸入臭氧还会降低吞噬作用和一氧化氮生成，并刺激肺灌洗细胞分泌内皮素 - 1，但不会改变巨噬细胞炎性蛋白 - 2的分泌。同时暴露于颗粒物会增强臭氧诱导的中央腺泡间隔细胞增多，但通过肺灌洗检测到的与臭氧相关的肺泡中性粒细胞增多和蛋白质通透性并未出现可测量的加重情况。间隔增厚增强与肺灌洗细胞中巨噬细胞炎性蛋白 - 2和内皮素 - 1的生成增加有关。有趣的是，吸入城市颗粒物会增加血浆内皮素 - 1水平，但这种反应不受臭氧和颗粒物对中心腺泡间隔组织变化的协同作用影响。这表明远端分布的颗粒物剂量对血管收缩剂的毛细血管内皮生成或过滤有影响。总体而言，单次暴露或连续三天每日暴露于污染物后观察到了等效的效应模式。实验数据与臭氧和可吸入颗粒物对肺部急性影响的流行病学证据一致，并提示了颗粒物暴露可能诱发心血管效应的一种可能机制。从广义上讲，环境空气中可吸入颗粒物的急性生物学效应似乎与旁分泌/内分泌干扰机制有关。
