Macrophages play a fundamental role in the different stages of muscle regeneration although the precise mechanisms involved are not entirely understood. Here we investigated the types of macrophages and cytokines that appeared in muscles after local gamma irradiation of mini-pigs that underwent no subsequent treatment or received three successive adipose tissue-derived stem cell (ASC) injections. Although some variability was observed among the three animals included in each study group, a general picture emerged. No macrophages appeared in control muscles from regions that had not been irradiated nor in muscles from irradiated regions derived from two animals. A third irradiated, but untreated animal, with characteristic muscle fibrosis and necrosis due to irradiation, showed invasion of M2 macrophages within small muscle lesions. In contrast, among the three ASC-treated and irradiated animals, one of them had completely recovered normal muscle architecture at the time of sampling with no invading macrophages, muscle from a second one contained mostly M1 macrophages and some M2-like macrophages whereas muscle from a third one displayed granulomas and giant cells. ASC treatment was associated with the presence of similar levels of pro-inflammatory cytokines within the two animals in the process of muscle regeneration whereas the levels of IL-4 and IL-10 expression were distinct from one animal to another. Microspectrofluorimetry and in situ hybridization revealed strong expression of TGF-β1 and TNFα in regenerating muscle. Overall, the data confirm the critical role of macrophages in muscle regeneration and suggest the involvement of a complex network of cytokine expression for successful recovery.

中文翻译：

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辐射后肌肉再生过程中巨噬细胞、巨细胞和肉芽肿的表征

巨噬细胞在肌肉再生的不同阶段发挥着重要作用，尽管所涉及的确切机制尚不完全清楚。在这里，我们研究了在对未接受后续治疗或连续三次脂肪组织衍生干细胞 (ASC) 注射的小型猪进行局部伽马照射后肌肉中出现的巨噬细胞和细胞因子的类型。尽管在每个研究组中包括的三只动物之间观察到了一些差异，但出现了一般情况。在未受辐射区域的对照肌肉中以及来自两只动物的受辐射区域的肌肉中均未出现巨噬细胞。第三只经过辐照但未经处理的动物，由于辐照具有特征性的肌肉纤维化和坏死，显示 M2 巨噬细胞侵入小肌肉病变内。相比之下，在三只接受 ASC 治疗和照射的动物中，其中一只在采样时完全恢复了正常的肌肉结构，没有巨噬细胞侵入，第二只的肌肉主要含有 M1 巨噬细胞和一些 M2 样巨噬细胞，而第三只的肌肉显示肉芽肿和巨细胞。ASC 治疗与肌肉再生过程中两只动物体内存在相似水平的促炎细胞因子有关，而 IL-4 和 IL-10 表达水平在一只动物与另一只动物之间不同。显微荧光光谱法和原位杂交显示 TGF-β1 和 TNFα 在再生肌肉中的强表达。全面的，