Activation of M1 macrophages plays a critical role in the initiation of acute lung injury
Activation of M1 macrophages plays a critical role in the initiation of acute lung injury
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DOI：
10.1042/bsr20171555
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发表时间：
2018-04-27
影响因子：
4
通讯作者：
Guo, Yu-Biao
中科院分区：
文献类型：
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作者：
Lu, Hui-Lun;Huang, Xin-Yan;Guo, Yu-Biao
本研究的目的是探讨M1巨噬细胞在急性肺损伤（ALI）中的作用。为了解决这个问题，我们使用脂多糖（LPS）处理的野生型和CD 11b-DTR小鼠，并检查其M1巨噬细胞水平，以及炎症和肺损伤的程度。此外，我们通过测量浸润的M1巨噬细胞中SP-A和SP-B的表达来评估肺功能。最后，我们将小鼠II型样肺泡上皮细胞（AT-II）和小鼠肺微血管内皮细胞（PMEC）与M1巨噬细胞在TNF-α或H2 O2的存在下共培养，并评估它们的活力和凋亡。LPS处理后，我们观察到肺M1/M2巨噬细胞的数量和血清白细胞介素-1 β（IL-1 β）、肿瘤坏死因子α（TNF-α）和活性氧（ROS）水平显著增加。此外，细胞因子的增加伴随着肺损伤的开始，其由SP-A和SP-B水平的降低指示。在去除巨噬细胞的CD 11b-DTR小鼠中，ALI减轻，血清IL-1 β、TNF-α和ROS水平降低，肺单核细胞趋化蛋白-1（MCP-1）和巨噬细胞炎性蛋白-2（MIP-2）水平降低。给予TNF-α和H2 O2后，M1巨噬细胞对AT-Ⅱ或PMEC的促凋亡作用显著增强，细胞活力显著降低，凋亡显著增加。我们的研究结果表明，M1巨噬细胞被招募到肺部，在那里它们显著促进TNF-α和ROS产生的增加，从而引发ALI。
The goal of the present study was to investigate the role of M1 macrophages in acute lung injury (ALI). To address this, we used lipopolysaccharide (LPS)-treated wild-type and CD11b-DTR mice, and examined their M1 macrophage levels, and the extent of their inflammation and pulmonary injuries. In addition, we evaluated pulmonary function by measuring the expressions of SP-A and SP-B in infiltrated M1 macrophages. Finally, we co-cultured the mouse type II-like alveolar epithelial cells (AT-II) and mouse pulmonary microvascular endothelial cells (PMECs) with M1 macrophages in the presence of TNF-alpha or H2O2 and assessed them for viability and apoptosis. After LPS treatment, we observed that the number of pulmonary M1/M2 macrophages and the serum levels of interleukin-1 beta (IL-1 beta), tumor necrosis factor a (TNF-alpha), and reactive oxygen species (ROS) significantly increased. Furthermore, the increase in cytokines was accompanied with the initiation of lung injury indicated by the decreased levels of SP-A and SP-B. In macrophage-depleted CD11b-DTR mice, ALI was attenuated, serum levels of IL-1 beta, TNF-alpha and ROS were reduced, and lung levels of monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-2 (MIP-2) were decreased. After administering TNF-alpha and H2O2, the proapoptotic effect of M1 macrophages on AT-II or PMECs significantly increased, the cell viabilities significantly decreased, and apoptosis significantly increased. Our results suggest that M1 macrophages are recruited to the lungs where they significantly contribute to an increase in TNF-alpha and ROS production, thus initiating ALI.