Inhibition of FasL sustains phagocytic cells and delays myogenesis in regenerating muscle fibers
Inhibition of FasL sustains phagocytic cells and delays myogenesis in regenerating muscle fibers
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FasL 的抑制可维持吞噬细胞并延迟再生肌纤维的肌生成
DOI：
10.1189/jlb.69.3.482
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发表时间：
2001
影响因子：
5.5
通讯作者：
U. Carraro
中科院分区：
文献类型：
--
作者：
M. Sandri;C. Sandri;Barbara Brun;E. Giurisato;M. Cantini;K. Rossini;C. Destro;P. Arslan;U. Carraro
巨噬细胞-肌肉细胞的相互作用是复杂的，大多数是未知的。骨骼肌中炎性细胞的持续存在可能对肌纤维活力至关重要。在本文中，我们表明，FasL在肌肉炎症的决议中发挥作用。我们分析了从第3天到第8天用FasL抑制剂（Fas-IG）或对照IG治疗的正常小鼠的发炎肌肉。在第3、5和10天收集处理的肌肉。重组Fas-IG蛋白治疗在损伤后5天（115，000 ± 27，838 vs. 41，661 ±6848，p<0.01）和10天（145，500 ± 40，850 vs. 5000±1000，p<0.001）诱导了严重的炎性细胞持续存在。肌纤维再生严重受损（37±14 vs. 252±28，p<0.01）。在Fas-IG处理期间，吞噬细胞的凋亡不存在（0.9±0.6 vs. 1300±150，p<0.0001），但是凋亡的单核细胞出现在Fas-IG施用悬浮液后第10天。在肌肉炎症过程中，在mRNA和蛋白质水平上，FasL表达的时间过程揭示了成肌细胞增殖过程中的峰值。FasL表达高峰与吞噬细胞凋亡高峰相一致。原位杂交显示FasL和MyoD mRNA在单核细胞中共表达，即，成肌细胞成肌细胞培养实验证实成肌细胞中有FasL的表达。此处显示的结果表明了控制成肌细胞-巨噬细胞相互作用的途径之一，并且可能与肌肉组织中炎症细胞的控制相关。也许用重组蛋白改变FasL表达可以改善退行性肌病中的炎症并上调肌肉再生。
Macrophage‐muscle cell interactions are complex, and the majority is unknown. The persistence of inflammatory cells in skeletal muscle could be critical for myofiber viability. In the present paper, we show that FasL plays a role in the resolution of muscle inflammation. We analyzed inflamed muscles of normal mice treated from day 3 to day 8 with a FasL inhibitor (Fas‐Ig) or with control Ig. Treated muscles were collected at 3, 5, and 10 days. The treatment with recombinant Fas‐Ig protein induced a severe persistence of inflammatory cells at 5 days (115,000±27,838 vs. 41,661±6848, p<0.01) and 10 days from injury (145,500±40,850 vs. 5000±1000, p<0.001). Myofiber regeneration was highly impaired (37±14 vs. 252±28, p<0.01). Apoptosis of phagocytic cells was absent during Fas‐Ig treatment (0.9±0.6 vs. 1300±150,p<0.0001), but apoptotic, mononucleated cells appeared at day 10, 2 days after the suspension of Fas‐Ig administration. The time course of FasL expression during muscle inflammation, at mRNA and protein level, reveals a peak during myoblast proliferation. The peak of FasL expression coincides with the peak of apoptosis of phagocytic cells. In situ hybridization shows the co‐expression of FasL and MyoD mRNA in mononucleated cells, i.e., myoblasts. Experiments on the myoblast cell culture confirmed the expression of FasL in myoblasts. The findings shown here indicate one of the pathways to control myoblast‐macrophage interaction and might be relevant for the control of inflammatory cells in muscle tissue. Perhaps altering FasL expression with recombinant proteins could ameliorate inflammation in degenerative myopathies and up‐regulate muscle regeneration.