Anti-inflammatory macrophages improve skeletal muscle recovery from ischemia-reperfusion

被引:33
作者
Hammers, David W. [1 ]
Rybalko, Viktoriya [1 ]
Merscham-Banda, Melissa [1 ]
Hsieh, Pei-Ling [1 ]
Suggs, Laura J. [2 ]
Farrar, Roger P. [1 ]
机构
[1] Univ Texas Austin, Dept Kinesiol, Austin, TX 78712 USA
[2] Univ Texas Austin, Dept Biomed Engn, Austin, TX 78712 USA
基金
美国国家卫生研究院;
关键词
reperfusion; macrophage; myogenesis; regenerative medicine; flow cytometry; GROWTH-FACTOR-I; PLASMINOGEN-ACTIVATOR; GENE-EXPRESSION; ALTERED INFLAMMATION; CCR2-/-MICE; IGF-I; REGENERATION; INJURY; MONOCYTES; MYOBLASTS;
D O I
10.1152/japplphysiol.00313.2014
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
The presence of macrophages (MPs) is essential for skeletal muscle to properly regenerate following injury. The aim of this study was the evaluation of MP profiles and their importance in skeletal muscle recovering from tourniquet-induced ischemia-reperfusion (I/R). Using flow cytometry, we identified two distinct CD11b(+) MP populations that differ in expression of the surface markers Ly-6C and F4/80. These populations are prominent at 3 and 5 days of reperfusion and molecularly correspond to inflammatory and anti-inflammatory MP phenotypes. Sorted MP populations demonstrated high levels of IGF-I expression, and whole muscle post-I/R IGF-I expression strongly correlates with F4/80 expression. This suggests MPs largely influence postinjury IGF-I upregulation. We additionally demonstrate that direct intramuscular injection of FACS-isolated CD11b(+)Ly-6C(lo)F4/80(hi) MPs improves the functional and histological recovery of I/R-affected muscle. Taken together, these data further support the substantial influence of the innate immune system on muscle regeneration and suggest MP-focused therapeutic approaches may greatly facilitate skeletal muscle recovery from substantial injury.
引用
收藏
页码:1067 / 1074
页数:8
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