The human heart contains distinct macrophage subsets with divergent origins and functions

被引：568

作者：

Bajpai, Geetika ^{[1
]}

Schneider, Caralin ^{[1
]}

Wong, Nicole ^{[1
]}

Bredemeyer, Andrea ^{[1
]}

Hulsmans, Maarten ^{[2
]}

Nahrendorf, Matthias ^{[2
]}

Epelman, Slava ^{[3
]}

Kreisel, Daniel ^{[4
]}

Liu, Yongjian ^{[5
]}

Itoh, Akinobu ^{[4
]}

Shankar, Thirupura S. ^{[6
]}

Selzman, Craig H. ^{[6
,7
]}

Drakos, Stavros G. ^{[6
,8
]}

Lavine, Kory J. ^{[1
,9
,10
]}

机构：

[1] Washington Univ, Sch Med, Dept Med, Ctr Cardiovasc Res,Div Cardiol, St Louis, MO 63110 USA

[2] Harvard Med Sch, Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA USA

[3] Univ Toronto, Toronto Gen Hosp, Peter Munk Cardiac Ctr, Ted Rogers Ctr Heart Failure Res, Toronto, ON, Canada

[4] Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA

[5] Washington Univ, Sch Med, Dept Radiol, St Louis, MO 63110 USA

[6] Univ Utah, Sch Med, Nora Eccles Harrison Cardiovasc Res & Training In, Salt Lake City, UT USA

[7] Univ Utah, Sch Med, Div Cardiothorac Surg, Salt Lake City, UT USA

[8] Univ Utah, Sch Med, Div Cardiovasc Med, Salt Lake City, UT USA

[9] Washington Univ, Sch Med, Dept Dev Biol, St Louis, MO 63130 USA

[10] Washington Univ, Sch Med, Dept Immunol & Pathol, St Louis, MO 63130 USA

来源：

NATURE MEDICINE | 2018年 / 24卷 / 08期

基金：

美国国家卫生研究院;

关键词：

TISSUE-RESIDENT MACROPHAGES; HEMATOPOIETIC STEM-CELLS; STEADY-STATE; CARDIAC MACROPHAGES; LANGERHANS CELLS; ANALYSIS REVEALS; DENDRITIC CELLS; LYMPH-NODES; MONOCYTES; EXPRESSION;

D O I：

10.1038/s41591-018-0059-x

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Paradigm-shifting studies in the mouse have identified tissue macrophage heterogeneity as a critical determinant of immune responses. In contrast, surprisingly little is known regarding macrophage heterogeneity in humans. Macrophages within the mouse heart are partitioned into CCR2- and CCR2+ subsets with divergent origins, repopulation mechanisms, and functions. Here, we demonstrate that the human myocardium also contains distinct subsets of CCR2- and CCR2+ macrophages. Analysis of sex-mismatched heart transplant recipients revealed that CCR2- macrophages are a tissue-resident population exclusively replenished through local proliferation, whereas CCR2+ macrophages are maintained through monocyte recruitment and proliferation. Moreover, CCR2- and CCR2+ macrophages have distinct functional properties, analogous to reparative CCR2- and inflammatory CCR2+ macrophages in the mouse heart. Clinically, CCR2+ macrophage abundance is associated with left ventricular remodeling and systolic function in heart failure patients. Collectively, these observations provide initial evidence for the functional importance of macrophage heterogeneity in the human heart.

引用

页码：1234 / +

页数：13

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