T细胞在调节丙烯醛诱导的肺部炎症和上皮细胞病理中的作用。

Michael T Borchers, Scott C Wesselkamper, Hitesh Deshmukh, Erin Beckman, Mario Medvedovic, Maureen Sartor, George D Leikauf
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引用次数: 0

摘要

在城市环境中接触丙烯醛对人体健康构成相当大的危害。丙烯醛暴露引起气道炎症,间质中单核细胞、巨噬细胞和淋巴细胞积聚,黏液细胞化生,气道扩大。目前,控制这些事件的机制尚不清楚,暴露于空气有毒物质后,t细胞亚群对肺部病理的相对贡献尚不清楚。在这项研究中,我们使用了一个由丙烯醛反复暴露诱导的肺部病理小鼠模型来研究肺淋巴细胞亚群是否对炎症细胞积累和上皮细胞病理有差异调节。为了研究淋巴细胞亚群的作用,我们使用了基因缺陷的转基因小鼠,并测量了与反复吸入2.0 ppm或0.5 ppm丙烯醛相关的几种细胞、分子和病理结果的变化。为了研究淋巴细胞亚群的潜在功能,我们从反复暴露于2.0 ppm丙烯醛的小鼠肺组织中纯化了这些细胞,分离并扩增了信使RNA (mRNA*)转录物,并进行了寡核苷酸微阵列分析。我们的数据表明,α - T细胞主要负责丙烯醛暴露后巨噬细胞的积累,而γ - T细胞是丙烯醛反复暴露后上皮细胞稳态的主要调节因子。这些发现得到了微阵列分析结果的支持,表明两个t细胞亚群在丙烯醛暴露后具有不同的基因表达谱。这些数据提供了强有力的证据,证明肺中的t细胞亚群是肺毒物暴露反应的主要决定因素,并表明阐明这些细胞在肺病理生理调节中的效应功能是有利的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The role of T cells in the regulation of acrolein-induced pulmonary inflammation and epithelial-cell pathology.

Exposure to acrolein in the ambient air in urban environments represents a considerable hazard to human health. Acrolein exposure causes airway inflammation, accumulation of monocytes, macrophages, and lymphocytes in the interstitium, mucous-cell metaplasia, and airspace enlargement. Currently, the mechanisms that control these events are unclear, and the relative contribution of T-cell subpopulations to pulmonary pathology after exposure to air toxics is unknown. In this study, we used a mouse model of pulmonary pathology induced by repeated acrolein exposure to examine whether pulmonary lymphocyte subpopulations differentially regulate inflammatory-cell accumulation and epithelial-cell pathology. To examine the role of the lymphocyte subpopulations, we used transgenic mice genetically deficient in either alphabeta T cells or gammadelta T cells and measured changes in several cellular, molecular, and pathologic outcomes associated with repeated inhalation exposure to 2.0 ppm or 0.5 ppm acrolein. To examine the potential functions of the lymphocyte subpopulations, we purified these cells from lung tissue of mice repeatedly exposed to 2.0 ppm acrolein, isolated and amplified the messenger RNA (mRNA*) transcripts, and performed oligonucleotide microarray analysis. Our data demonstrate that alphabeta T cells are primarily responsible for the accumulation of macrophages after acrolein exposure, whereas gammadelta T cells are the primary regulators of epithelial-cell homeostasis after repeated acrolein exposure. These findings are supported by the results of microarray analyses indicating that the two T-cell subpopulations have distinct gene-expression profiles after acrolein exposure. These data provide strong evidence that the T-cell subpopulations in the lung are major determinants of the response to pulmonary toxicant exposure and suggest that it is advantageous to elucidate the effector functions of these cells in the modulation of lung pathophysiology.

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