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Adiponectin primes human monocytes into alternative anti-inflammatory M2 macrophages.

ABSTRACT: 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.

SUBMITTER: Lovren F

PROVIDER: S-EPMC2944489 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

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Adiponectin primes human monocytes into alternative anti-inflammatory M2 macrophages.

Lovren Fina F Pan Yi Y Quan Adrian A Szmitko Paul E PE Singh Krishna K KK Shukla Praphulla C PC Gupta Milan M Chan Lawrence L Al-Omran Mohammed M Teoh Hwee H Verma Subodh S

American journal of physiology. Heart and circulatory physiology 20100709 3

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-infla ...[more]

PMID: 20622108

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Adiponectin primes human monocytes into alternative anti-inflammatory M2 macrophages.

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Adiponectin primes human monocytes into alternative anti-inflammatory M2 macrophages.

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