Macrophages Facilitate Electrical Conduction in the Heart

被引：773

作者：

Hulsmans, Maarten ^{[1
]}

Clauss, Sebastian ^{[2
,3
,4
]}

Xiao, Ling ^{[2
]}

Aguirre, Aaron D. ^{[1
,2
]}

King, Kevin R. ^{[1
]}

Hanley, Alan ^{[2
,5
]}

Hucker, William J. ^{[2
]}

Wuelfers, Eike M. ^{[6
,7
]}

Seemann, Gunnar ^{[6
,7
]}

Courties, Gabriel ^{[1
]}

Iwamoto, Yoshiko ^{[1
]}

Sun, Yuan ^{[1
]}

Savol, Andrej J. ^{[8
]}

Sager, Hendrik B. ^{[1
]}

Lavine, Kory J. ^{[9
]}

Fishbein, Gregory A. ^{[10
]}

Capen, Diane E. ^{[1
]}

Da Silva, Nicolas ^{[1
]}

Miquerol, Lucile ^{[11
]}

Wakimoto, Hiroko ^{[12
]}

Seidman, Christine E. ^{[12
,13
,14
]}

Seidman, Jonathan G. ^{[12
]}

Sadreyev, Ruslan I. ^{[8
,15
]}

Naxerova, Kamila ^{[12
]}

Mitchell, Richard N. ^{[10
]}

Brown, Dennis ^{[1
]}

Libby, Peter ^{[13
]}

Weissleder, Ralph ^{[1
,16
]}

Swirski, Filip K. ^{[1
]}

Kohl, Peter ^{[6
,17
]}

Vinegoni, Claudio ^{[1
]}

Milan, David J. ^{[2
,18
,19
]}

Ellinor, Patrick T. ^{[2
,18
,19
]}

Nahrendorf, Matthias ^{[1
,2
]}

机构：

[1] Harvard Med Sch, Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA

[2] Harvard Med Sch, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA

[3] Univ Munich, Univ Hosp Munich, Dept Med, Campus Grosshadern, D-81377 Munich, Germany

[4] Partner Site Munich, DZHK German Ctr Cardiovascular Res, Munich, Germany

[5] Natl Univ Ireland Galway, Cardiovasc Res Ctr, Galway, Ireland

[6] Univ Heart Ctr Freiburg, Inst Expt Cardiovasc Med, D-79110 Freiburg, Germany

[7] Univ Freiburg, Fac Med, D-79110 Freiburg, Germany

[8] Harvard Med Sch, Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA

[9] Washington Univ, Ctr Cardiovasc Res, St Louis, MO 63110 USA

[10] Harvard Med Sch, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA

[11] Aix Marseille Univ, CNRS, IBDM, F-13288 Marseille, France

[12] Harvard Med Sch, Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA

[13] Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Div Cardiovasc Med, Boston, MA 02115 USA

[14] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA

[15] Harvard Med Sch, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA

[16] Harvard Med Sch, Dept Syst Biol, Boston, MA 02115 USA

[17] Imperial Coll London, Natl Heart & Lung Inst, Cardiac Biophys & Syst Biol, London SW3 6NP, England

[18] Broad Inst Harvard, Program Populat & Med Genet, Cambridge, MA 02142 USA

[19] MIT, Cambridge, MA 02142 USA

来源：

CELL | 2017年 / 169卷 / 03期

基金：

欧洲研究理事会;

关键词：

ATRIOVENTRICULAR NODE; MYOCARDIAL-INFARCTION; CARDIAC MACROPHAGES; TISSUE MACROPHAGES; MEMBRANE CHANNEL; GAP-JUNCTIONS; IMMUNE-SYSTEM; STEADY-STATE; MYOCYTES; CELLS;

D O I：

10.1016/j.cell.2017.03.050

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Organ-specific functions of tissue-resident macrophages in the steady-state heart are unknown. Here, we show that cardiac macrophages facilitate electrical conduction through the distal atrioventricular node, where conducting cells densely intersperse with elongated macrophages expressing connexin 43. When coupled to spontaneously beating cardiomyocytes via connexin-43-containing gap junctions, cardiac macrophages have a negative resting membrane potential and depolarize in synchrony with cardiomyocytes. Conversely, macrophages render the resting membrane potential of cardiomyocytes more positive and, according to computational modeling, accelerate their repolarization. Photostimulation of channelrhodopsin-2-expressing macrophages improves atrioventricular conduction, whereas conditional deletion of connexin 43 in macrophages and congenital lack of macrophages delay atrioventricular conduction. In the Cd11b(DTR) mouse, macrophage ablation induces progressive atrioventricular block. These observations implicate macrophages in normal and aberrant cardiac conduction.

引用

页码：510 / +

页数：33

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