Adiponectin primes human monocytes into alternative anti-inflammatory M2 macrophages
Adiponectin primes human monocytes into alternative anti-inflammatory M2 macrophages
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DOI：
10.1152/ajpheart.00115.2010
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发表时间：
2010-09-01
影响因子：
4.8
通讯作者：
Verma, Subodh
中科院分区：
文献类型：
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作者：
Lovren, Fina;Pan, Yi;Verma, Subodh
Lovren F，PanY，Quan A，Szmitko PE，Singh KK，Shukla PC，Gupta M，Chan L，Al-Omran M，Teoh H，Verma S.脂联素将人单核细胞转化为替代的抗炎M2巨噬细胞。Am J Physiol心脏圈Physiol 299：H656-H663,2010。2010年7月9日首次出版；doi：10.1152/ajpheart.00115.2010。-巨噬细胞动力学改变是内脏肥胖引发炎症和心脏代谢风险的关键机制。由于单核细胞可以分化为致动脉粥样硬化的M1巨噬细胞或抗炎的M2巨噬细胞，限制M1而促进M2分化的方法代表了一种独特的治疗策略。我们推测，脂联素可能使人类单核细胞向M2表型转化。脂联素促进人类单核细胞交替激活为抗炎M2巨噬细胞，而不是经典激活的M1表型。脂联素处理的细胞表现出增加的M2标记，包括甘露糖受体(MR)和替代巨噬细胞激活相关的CC趋化因子-1。M_1巨噬细胞与脂联素处理的M_2培养上清液孵育后，肿瘤坏死因子-α和单核细胞趋化蛋白-1的分泌受到明显抑制。人单核细胞通过脂联素激活M2巨噬细胞，并通过PPAR-α介导AMP激活的蛋白激酶和PPAR-γ。此外，从脂联素基因敲除小鼠分离的巨噬细胞显示M2标记物的水平降低，如MR，这些标记物可以通过脂联素治疗恢复。我们报道了一种新的免疫调节机制，通过脂联素促进人单核细胞分化为抗炎的M2巨噬细胞。与低脂联素水平相关的情况，如内脏肥胖和胰岛素抵抗，可能会促进动脉粥样硬化，部分是通过异常的巨噬细胞动力学。
Lovren F, Pan Y, Quan A, Szmitko PE, Singh KK, Shukla PC, Gupta M, Chan L, Al-Omran M, Teoh H, Verma S. Adiponectin primes human monocytes into alternative anti-inflammatory M2 macrophages. Am J Physiol Heart Circ Physiol 299: H656-H663, 2010. First published July 9, 2010; doi:10.1152/ajpheart.00115.2010.-Altered macrophage kinetics is a pivotal mechanism of visceral obesity-induced inflammation and cardiometabolic risk. Because monocytes can differentiate into either proatherogenic M1 macrophages or anti-inflammatory M2 macrophages, approaches that limit M1 while promoting M2 differentiation represent a unique therapeutic strategy. We hypothesized that adiponectin may prime human monocytes toward the M2 phenotype. Adiponectin promoted the alternative activation of human monocytes into anti-inflammatory M2 macrophages as opposed to the classically activated M1 phenotype. Adiponectin-treated cells displayed increased M2 markers, including the mannose receptor (MR) and alternative macrophage activation-associated CC chemokine-1. Incubation of M1 macrophages with adiponectin-treated M2-derived culture supernatant resulted in a pronounced inhibition of tumor necrosis factor-alpha and monocyte chemotactic protein-1 secretion. Activation of human monocytes into M2 macrophages by adiponectin was mediated, in addition to AMP-activated protein kinase and peroxisome proliferator-activated receptor (PPAR)-gamma, via PPAR-alpha. Furthermore, macrophages isolated from adiponectin knockout mice demonstrated diminished levels of M2 markers such as MR, which were restored with adiponectin treatment. We report a novel immunoregulatory mechanism through which adiponectin primes human monocyte differentiation into anti-inflammatory M2 macrophages. Conditions associated with low adiponectin levels, such as visceral obesity and insulin resistance, may promote atherosclerosis, in part through aberrant macrophage kinetics.