Miller Lisa A, Gerriets Joan E, Tyler Nancy K, Abel Kristina, Schelegle Edward S, Plopper Charles G, Hyde Dallas M
Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine, University of California, Davis, CA 95616, USA.
Toxicol Appl Pharmacol. 2009 Apr 1;236(1):39-48. doi: 10.1016/j.taap.2008.12.031. Epub 2009 Feb 7.
The epidemiologic link between air pollutant exposure and asthma has been supported by experimental findings, but the mechanisms are not understood. In this study, we evaluated the impact of combined ozone and house dust mite (HDM) exposure on the immunophenotype of peripheral blood and airway lymphocytes from rhesus macaque monkeys during the postnatal period of development. Starting at 30 days of age, monkeys were exposed to 11 cycles of filtered air, ozone, HDM aerosol, or ozone+HDM aerosol. Each cycle consisted of ozone delivered at 0.5 ppm for 5 days (8 h/day), followed by 9 days of filtered air; animals received HDM aerosol during the last 3 days of each ozone exposure period. Between 2-3 months of age, animals co-exposed to ozone+HDM exhibited a decline in total circulating leukocyte numbers and increased total circulating lymphocyte frequency. At 3 months of age, blood CD4+/CD25+ lymphocytes were increased with ozone+HDM. At 6 months of age, CD4+/CD25+ and CD8+/CD25+ lymphocyte populations increased in both blood and lavage of ozone+HDM animals. Overall volume of CD25+ cells within airway mucosa increased with HDM exposure. Ozone did not have an additive effect on volume of mucosal CD25+ cells in HDM-exposed animals, but did alter the anatomical distribution of this cell type throughout the proximal and distal airways. We conclude that a window of postnatal development is sensitive to air pollutant and allergen exposure, resulting in immunomodulation of peripheral blood and airway lymphocyte frequency and trafficking.
空气污染物暴露与哮喘之间的流行病学联系已得到实验结果的支持,但其机制尚不清楚。在本研究中,我们评估了产后发育期间,猕猴同时暴露于臭氧和屋尘螨(HDM)对其外周血和气道淋巴细胞免疫表型的影响。从30日龄开始,将猕猴暴露于11个周期的过滤空气、臭氧、HDM气溶胶或臭氧+HDM气溶胶中。每个周期包括以0.5 ppm的浓度输送臭氧5天(每天8小时),随后是9天的过滤空气;动物在每个臭氧暴露期的最后3天接受HDM气溶胶。在2至3个月大时,同时暴露于臭氧+HDM的动物循环白细胞总数下降,循环淋巴细胞总频率增加。在3个月大时,臭氧+HDM组血液中CD4+/CD25+淋巴细胞增加。在6个月大时,臭氧+HDM组动物的血液和灌洗液中CD4+/CD25+和CD8+/CD25+淋巴细胞群体均增加。气道黏膜内CD25+细胞的总体积随HDM暴露而增加。臭氧对HDM暴露动物黏膜CD25+细胞的体积没有叠加作用,但确实改变了这种细胞类型在整个近端和远端气道的解剖分布。我们得出结论,产后发育的一个窗口期对空气污染物和过敏原暴露敏感,导致外周血和气道淋巴细胞频率及转运的免疫调节。