Tidball James G, Wehling-Henricks Michelle
Department of Physiological Science, 5833 Life Science Building, University of California, Los Angeles, CA 90095, USA.
J Physiol. 2007 Jan 1;578(Pt 1):327-36. doi: 10.1113/jphysiol.2006.118265. Epub 2006 Oct 12.
Muscle injury or modified muscle use can stimulate muscle invasion by leucocytes that have the potential to increase tissue damage or promote tissue growth and repair. In the present investigation, we examined the role of macrophages in muscle injury, repair and regeneration during modified muscle loading. Weight-bearing was removed from the hindlimbs of mice for 10 days followed by reloading through normal ambulation. During the unloading period, soleus muscle fibre cross-section decreased by 38%. Prior to the onset of reloading, mice received a series of intraperitoneal injections of anti-F4/80, which binds a mouse macrophage surface antigen. Although anti-F4/80 injections did not affect macrophage numbers in soleus muscles at 2 days of reloading, macrophages were reduced by 86% at 4 days of reloading. Muscle membrane lysis during the reloading period did not differ at 2 days of reloading between anti-F4/80-treated mice and mice that received isotype control antibody. However, control animals showed large decreases in the number of fibres with membrane lesions at 4 days of reloading, but this membrane repair did not occur in macrophage-depleted mice. Macrophage-depletion also reduced muscle regeneration (indicated by central nucleation) and satellite cell differentiation (indicated by reductions in MyoD-expressing satellite cells) and prevented growth of muscle fibres that normally occurred in control animals between days 2 and 4 of reloading. These findings collectively show that macrophages play a significant role in muscle fibre membrane repair, regeneration and growth during increased muscle use after a period of atrophy.
肌肉损伤或改变的肌肉使用方式可刺激白细胞侵入肌肉，这些白细胞有可能增加组织损伤或促进组织生长与修复。在本研究中，我们研究了巨噬细胞在改变肌肉负荷期间的肌肉损伤、修复和再生中的作用。将小鼠后肢去负荷10天，然后通过正常行走重新加载负荷。在去负荷期间，比目鱼肌纤维横截面积减少了38%。在重新加载负荷开始前，小鼠接受了一系列腹腔注射抗F4/80，该抗体可结合小鼠巨噬细胞表面抗原。尽管抗F4/80注射在重新加载负荷2天时对比目鱼肌中的巨噬细胞数量没有影响，但在重新加载负荷4天时巨噬细胞减少了86%。在重新加载负荷2天时，抗F4/80处理的小鼠与接受同型对照抗体的小鼠之间，重新加载负荷期间的肌膜溶解情况没有差异。然而，对照动物在重新加载负荷4天时，出现膜损伤的纤维数量大幅减少，但巨噬细胞耗竭的小鼠并未发生这种膜修复。巨噬细胞耗竭还减少了肌肉再生（以中央核化表示）和卫星细胞分化（以表达MyoD的卫星细胞减少表示），并阻止了对照动物在重新加载负荷第2天至第4天期间正常发生的肌纤维生长。这些研究结果共同表明，巨噬细胞在一段时间萎缩后增加肌肉使用期间的肌纤维膜修复、再生和生长中发挥着重要作用。
