The role of T cells in the regulation of acrolein-induced pulmonary inflammation and epithelial-cell pathology.
The role of T cells in the regulation of acrolein-induced pulmonary inflammation and epithelial-cell pathology.
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发表时间：
2009-12
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通讯作者：
M. Borchers;S. Wesselkamper;H. Deshmukh;E. Beckman;M. Medvedovic;M. Sartor;G. Leikauf
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作者：
M. Borchers;S. Wesselkamper;H. Deshmukh;E. Beckman;M. Medvedovic;M. Sartor;G. Leikauf
在城市环境中暴露于环境空气中的丙烯醛对人类健康具有相当大的危害。丙烯醛暴露导致气道炎症，单核细胞、巨噬细胞和淋巴细胞在肺泡中积聚，粘液细胞化生和气道扩大。目前，控制这些事件的机制尚不清楚，T细胞亚群在暴露于空气毒物后对肺部病理的相对贡献尚不清楚。在这项研究中，我们使用了一个小鼠模型，反复丙烯醛暴露诱导的肺部病理检查是否肺淋巴细胞亚群差异调节炎症细胞的积累和上皮细胞的病理。为了研究淋巴细胞亚群的作用，我们使用了α T细胞或γ δ T细胞遗传缺陷的转基因小鼠，并测量了与反复吸入暴露于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这些细胞，分离并扩增信使RNA（mRNA*）转录物，并进行寡核苷酸微阵列分析。我们的数据表明，α T细胞是主要负责丙烯醛暴露后的巨噬细胞的积累，而γ δ T细胞是反复丙烯醛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表明，在肺中的T细胞亚群是肺毒物暴露的反应的主要决定因素，并建议，这是有利的，以阐明这些细胞在肺病理生理学的调制的效应器功能。
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.