Pulmonary Macrophage Subpopulations in the Induction and Resolution of Acute Lung Injury

Pulmonary Macrophage Subpopulations in the Induction and Resolution of Acute Lung Injury
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DOI:
10.1165/rcmb.2012-0090oc
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发表时间:
2012-10-01
影响因子:
6.4
通讯作者:
Manicone, Anne M.
Manicone, Anne M.
中科院分区:
医学1区
文献类型:
--
作者:
Johnston, Laura K.;Rims, Cliff R.;Manicone, Anne M.

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巨噬细胞是肺中炎症和修复反应的关键协调者,其功能的多样性由其极化状态和不同的亚群以及在肺中的定位指示。在这里,我们的特点是在诱导和解决铜绿假单胞菌感染引起的急性肺损伤的肺间质和肺泡室的巨噬细胞群体。我们根据细胞表面蛋白标志物的FACS分析,结合使用实时PCR进行基因表达的细胞分选,鉴定了巨噬细胞亚群和极性。通过这些技术,我们验证了一种新的,交替激活(M2)的标记物(转铁蛋白受体),我们描述了三个间质和肺泡巨噬细胞亚群在肺中的分布和功能状态演变的诱导肺损伤的决议阶段。总之,这些发现表明肺中不同巨噬细胞亚群的存在和演变,这些亚群在调节炎症反应及其消退中起特定作用。这些亚群平衡和功能的改变可能导致急性肺损伤。
Macrophages are key orchestrators of the inflammatory and repair responses in the lung, and the diversity of their function is indicated by their polarized states and distinct subpopulations and localization in the lung. Here, we characterized the pulmonary macrophage populations in the interstitial and alveolar compartments during the induction and resolution of acute lung injury induced by Pseudomonas aeruginosa infection. We identified macrophage subpopulations and polarity according to FACS analysis of cell surface protein markers, combined with cell sorting for gene expression using real-time PCR. With these techniques, we validated a novel, alternatively activated (M2) marker (transferrin receptor), and we described three interstitial and alveolar macrophage subpopulations in the lung whose distribution and functional state evolved from the induction to resolution phases of lung injury. Together, these findings indicate the presence and evolution of distinct macrophage subsets in the lung that serve specific niches in regulating the inflammatory response and its resolution. Alterations in the balance and function of these subpopulations could lead to nonresolving acute lung injury.