Adiponectin primes human monocytes into alternative anti-inflammatory M2 macrophages

被引：187

作者：

Lovren, Fina ^{[1
,2
]}

Pan, Yi ^{[1
]}

Quan, Adrian ^{[1
,2
]}

Szmitko, Paul E. ^{[2
,4
]}

Singh, Krishna K. ^{[1
,2
]}

Shukla, Praphulla C. ^{[1
,2
]}

Gupta, Milan ^{[1
,3
,6
,7
,8
]}

Chan, Lawrence ^{[9
,10
]}

Al-Omran, Mohammed ^{[11
,12
,13
]}

Teoh, Hwee ^{[1
,2
,3
,8
]}

Verma, Subodh ^{[1
,3
,5
,8
,13
]}

机构：

[1] St Michaels Hosp, Li Ka Shing Knowledge Inst, Keenan Res Ctr, Div Cardiac Surg, Toronto, ON M5B 1W8, Canada

[2] St Michaels Hosp, Li Ka Shing Knowledge Inst, Keenan Res Ctr, Translat Traineeship Program Atherosclerosis, Toronto, ON M5B 1W8, Canada

[3] St Michaels Hosp, Li Ka Shing Knowledge Inst, Keenan Res Ctr, Cardiometab Risk Initiat, Toronto, ON M5B 1W8, Canada

[4] Univ Toronto, Dept Med, Toronto, ON, Canada

[5] Univ Toronto, Dept Surg, Toronto, ON, Canada

[6] William Osler Hlth Ctr, Div Cardiol, Brampton, ON, Canada

[7] McMaster Univ, Dept Med, Hamilton, ON, Canada

[8] Canadian Cardiovasc Res Network, Brampton, ON, Canada

[9] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA

[10] Baylor Coll Med, Dept Med, Houston, TX 77030 USA

[11] King Saud Univ, Coll Med, Div Vasc Surg, Riyadh 11461, Saudi Arabia

[12] King Khalid Univ Hosp, Riyadh 11472, Saudi Arabia

[13] King Saud Univ, Li Ka Shing Collaborat Res Program, Riyadh, Saudi Arabia

来源：

AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY | 2010年 / 299卷 / 03期

基金：

美国国家卫生研究院;

关键词：

adiponectin; obesity; macrophage activation; C-REACTIVE PROTEIN; PLASMA-PROTEIN; ADIPOSE-TISSUE; PPAR-GAMMA; INFLAMMATION; ACTIVATION; EXPRESSION; MEDIATORS; OBESITY; ATHEROSCLEROSIS;

D O I：

10.1152/ajpheart.00115.2010

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：H656 / H663

页数：8

共 39 条

[1] Adipocyte-derived plasma protein adiponectin acts as a platelet-derived growth factor-BB-binding protein and regulates growth factor-induced common postreceptor signal in vascular smooth muscle cell [J].