Inflammatory monocytes recruited after skeletal muscle injury switch into antiinflammatory macrophages to support myogenesis.
Inflammatory monocytes recruited after skeletal muscle injury switch into antiinflammatory macrophages to support myogenesis.
复制标题
DOI：
10.1084/jem.20070075
复制
发表时间：
2007-05-14
期刊：
影响因子：
--
通讯作者：
Chazaud B
中科院分区：
文献类型：
--
作者：
Arnold L;Henry A;Poron F;Baba-Amer Y;van Rooijen N;Plonquet A;Gherardi RK;Chazaud B
巨噬细胞(MPS)在体内对骨骼肌再生具有重要作用，在体外可能通过促有丝分裂和抗凋亡作用对肌源性细胞的生长产生有益的影响。然而，MPS具有很强的通用性，可以根据其激活状态发挥各种功能，甚至相反的功能。我们研究了单核细胞(MO)/MP在骨骼肌修复过程中的表型和功能。在CX3CR1GFP/+小鼠体内，乳胶微珠选择性标记循环MOS表明，受损肌肉仅从血液中招募CX3CR1lo/Ly-6C+MOS，呈现不分裂的F4/80lo促炎症特征。然后，在肌肉内，这些细胞转换其表型成为增殖的抗炎细胞CX3CR1hi/Ly-6C−细胞，进一步分化为F4/80hi MPS。在体外，肌肉细胞碎片的吞噬诱导促炎MPS向释放转化生长因子β-1的抗炎表型转变。在共培养中，炎症性MPS刺激肌源性细胞增殖，而抗炎MPS表现出分化活性，通过肌生成素表达和肌管融合来评价。最后，损伤时CD11b-白喉毒素受体小鼠循环MOS的耗尽完全阻止了肌肉再生，而后期肌肉内F4/80HI MPS的耗尽则减少了再生纤维的直径。总而言之，受损的骨骼肌招募了表现出炎症特征的MOS，这些MOS具有吞噬功能，并迅速转化为抗炎MPS，从而刺激肌肉生成和纤维生长。
Macrophages (MPs) are important for skeletal muscle regeneration in vivo and may exert beneficial effects on myogenic cell growth through mitogenic and antiapoptotic activities in vitro. However, MPs are highly versatile and may exert various, and even opposite, functions depending on their activation state. We studied monocyte (MO)/MP phenotypes and functions during skeletal muscle repair. Selective labeling of circulating MOs by latex beads in CX3CR1GFP/+ mice showed that injured muscle recruited only CX3CR1lo/Ly-6C+ MOs from blood that exhibited a nondividing, F4/80lo, proinflammatory profile. Then, within muscle, these cells switched their phenotype to become proliferating antiinflammatory CX3CR1hi/Ly-6C− cells that further differentiated into F4/80hi MPs. In vitro, phagocytosis of muscle cell debris induced a switch of proinflammatory MPs toward an antiinflammatory phenotype releasing transforming growth factor β1. In co-cultures, inflammatory MPs stimulated myogenic cell proliferation, whereas antiinflammatory MPs exhibited differentiating activity, assessed by both myogenin expression and fusion into myotubes. Finally, depletion of circulating MOs in CD11b–diphtheria toxin receptor mice at the time of injury totally prevented muscle regeneration, whereas depletion of intramuscular F4/80hi MPs at later stages reduced the diameter of regenerating fibers. In conclusion, injured skeletal muscle recruits MOs exhibiting inflammatory profiles that operate phagocytosis and rapidly convert to antiinflammatory MPs that stimulate myogenesis and fiber growth.
登录
查看更多内容
影响因子：
4
作者：
GORDON, S
通讯作者：
GORDON, S
影响因子：
4.4
作者：
De Rossi, M;Bernasconi, P;Mantegazza, R
通讯作者：
Mantegazza, R
影响因子：
4.4
作者：
Fadok, VA;Bratton, DL;Henson, PM
通讯作者：
Henson, PM
影响因子：
5.5
作者：
Bondesen, BA;Mills, ST;Pavlath, GK
通讯作者：
Pavlath, GK
影响因子：
4.4
作者：
Broussard, SR;McCusker, RH;Kelley, KW
通讯作者：
Kelley, KW