Induction of M2 regulatory macrophages through the β2-adrenergic receptor with protection during endotoxemia and acute lung injury.
Induction of M2 regulatory macrophages through the β2-adrenergic receptor with protection during endotoxemia and acute lung injury.
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DOI：
10.1159/000358524
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发表时间：
2014
影响因子：
5.3
通讯作者：
Ward PA
中科院分区：
文献类型：
--
作者：
Grailer JJ;Haggadone MD;Sarma JV;Zetoune FS;Ward PA
急性炎症的主要驱动力是巨噬细胞，众所周知，巨噬细胞具有儿茶酚胺的受体。根据其功能，巨噬细胞大致分为M1(促炎)或M2(抗炎)表型。在这项研究中，我们研究了儿茶酚胺对激活的巨噬细胞表型的影响。在脂多糖(LPS)存在下，小鼠腹膜巨噬细胞获得了M1表型。然而，当内毒素与肾上腺素或去甲肾上腺素同时存在时，会导致M2表型增强，包括高水平的精氨酸酶-1和白介素10，而M1标志物的表达减少。此外，肾上腺素在体外可增强巨噬细胞的吞噬功能和促进2型T细胞反应，这是M2巨噬细胞的已知特征。M2亚型特异性标志物分析表明，内毒素和儿茶酚胺共同处理的巨噬细胞不是交替激活，而是调节性巨噬细胞亚型。有趣的是，儿茶酚胺通过β2肾上腺素能受体发出信号，而不是典型的cAMP/蛋白激酶A信号通路。相反，M2途径需要一个完整的磷酸肌醇3-激酶途径。在内毒素血症小鼠模型和脂多糖诱导的急性肺损伤模型中，阻断β-2肾上腺素能受体分别减少了小鼠的存活率和加重了损伤。这些结果证明了β-2肾上腺素能受体在促进M2巨噬细胞表型中的作用。
Main drivers of acute inflammation are macrophages, which are known to have receptors for catecholamines. Based on their function, macrophages are broadly categorized as either M1 (pro-inflammatory) or M2 phenotypes (anti-inflammatory). In this study, we investigated catecholamine-induced alterations in the phenotype of activated macrophages. In the presence of lipopolysaccharide (LPS), mouse peritoneal macrophages acquired an M1 phenotype. However, the co-presence of LPS and either epinephrine or norepinephrine resulted in a strong M2 phenotype including high levels of arginase-1 and interleukin (IL) -10, and reduced expression of M1 markers. Furthermore, epinephrine enhanced macrophage phagocytosis and promoted type 2 T cell responses in vitro, which are known features of M2 macrophages. Analysis of M2 subtype-specific markers indicated that LPS and catecholamine co-treated macrophages were not alternatively activated, but of the regulatory macrophage subtype. Interestingly, catecholamines signaled through the β2 adrenergic receptor, but not the canonical cAMP/protein kinase A signaling pathway. Instead, the M2 pathway required an intact phosphoinositol 3-kinase pathway. Blockade of the β2 adrenergic receptor reduced survival and enhanced injury during mouse models of endotoxemia and LPS-induced acute lung injury, respectively. These results demonstrate a role for the β2 adrenergic receptor in promoting the M2 macrophage phenotype.
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DOI：
10.1196/annals.1321.009
发表时间：
2004-01-01
期刊：
GLUCOCORTICOID ACTION: BASIC AND CLINICAL IMPLICATIONS
影响因子：
--
作者：
Franchimont, D
通讯作者：
Franchimont, D
影响因子：
6.1
作者：
Lin Ying;Zhu Xi;Chen Li
通讯作者：
Chen Li
DOI：
10.1038/nri3073
发表时间：
2011-10-14
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
4.4
作者：
Leidi, Marzia;Gotti, Elisa;Golay, Josee
通讯作者：
Golay, Josee
影响因子：
64.8
作者：
BOND, RA;LEFF, P;LEFKOWITZ, RJ
通讯作者：
LEFKOWITZ, RJ