Evidence for a prosurvival role of alpha-7 nicotinic acetylcholine receptor in alternatively (M2)-activated macrophages.
Evidence for a prosurvival role of alpha-7 nicotinic acetylcholine receptor in alternatively (M2)-activated macrophages.
复制标题
α-7烟碱乙酰胆碱受体在替代（M2）激活的巨噬细胞中发挥作用的证据。
DOI：
10.1002/phy2.189
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发表时间：
2013-12-01
影响因子：
2.5
通讯作者：
Vazquez, Guillermo
中科院分区：
文献类型：
--
作者：
Lee, Robert H;Vazquez, Guillermo
最近在内皮细胞和巨噬细胞中的观察表明，烟碱乙酰胆碱受体（nAChRs）是与动脉粥样硬化形成相关的机制中的潜在新参与者。在巨噬细胞中，α 7 nAChR介导抗炎作用，并有助于调节胆固醇流量和吞噬作用。考虑到巨噬细胞凋亡是动脉粥样硬化病变发展的所有阶段的关键过程，在本研究中，我们首次使用野生型和α 7 nAChR敲除小鼠的体外极化（M1和M2）骨髓源性巨噬细胞（BMDM）检查了α 7 nAChR表达和功能对巨噬细胞存活和凋亡的影响。我们的研究结果表明，刺激α 7 nAChR导致STAT 3促生存通路的激活，并保护巨噬细胞免受内质网（ER）应激诱导的凋亡。这些作用对于M2 BMDM是相当选择性的，并且与JAK 2/STAT 3轴的激活相关。值得注意的是，这些作用在缺乏α 7 nAChR的M2巨噬细胞中完全丧失。巨噬细胞凋亡是炎症性血管疾病各个阶段的关键过程。我们的研究首次使用来自野生型和α 7 nAChR敲除小鼠的体外极化（M1和M2）骨髓源性巨噬细胞（BMDM）检查了α 7 nAChR表达和功能对巨噬细胞存活和凋亡的影响。我们发现，刺激α 7 nAChR激活了STAT 3促生存通路，并保护巨噬细胞免受内质网应激诱导的凋亡，这种作用对M2巨噬细胞具有相当的选择性，在缺乏α 7 nAChR的M2巨噬细胞中完全丧失。
Recent observations in endothelial cells and macrophages indicate that nicotinic acetylcholine receptors (nAChRs) are potential novel players in mechanisms linked to atherogenesis. In macrophages, α7nAChR mediates anti‐inflammatory actions and contributes to regulation of cholesterol flux and phagocytosis. Considering that macrophage apoptosis is a key process throughout all stages of atherosclerotic lesion development, in the present study, we examined for the first time the impact of α7nAChR expression and function in macrophage survival and apoptosis using in vitro polarized (M1 and M2) bone marrow‐derived macrophages (BMDMs) from wild‐type and α7nAChR knockout mice. Our findings show that stimulation of α7nAChR results in activation of the STAT3 prosurvival pathway and protection of macrophages from endoplasmic reticulum (ER) stress‐induced apoptosis. These actions are rather selective for M2 BMDMs and are associated to activation of the JAK2/STAT3 axis. Remarkably, these effects are completely lost in M2 macrophages lacking α7nAChR. Macrophage apoptosis is a key process throughout all stages of inflammatory vascular disease. Our studies examine for the first time the impact of α7nAChR expression and function in macrophage survival and apoptosis using in vitro polarized (M1 and M2) bone marrow‐derived macrophages (BMDMs) from wild‐type and α7nAChR knockout mice. We show that stimulation of α7nAChR activates the STAT3 prosurvival pathway and protects macrophages from endoplasmic reticulum stress‐induced apoptosis, an effect rather selective for M2 macrophages and completely lost in M2 macrophages lacking α7nAChR.