Neutrophil-induced skeletal muscle damage: a calculated and controlled response following hindlimb unloading and reloading
Neutrophil-induced skeletal muscle damage: a calculated and controlled response following hindlimb unloading and reloading
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DOI：
10.1152/ajpregu.90318.2008
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发表时间：
2008-12-01
影响因子：
2.8
通讯作者：
Frenette, Jerome
中科院分区：
文献类型：
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作者：
Dumont, Nicolas;Bouchard, Patrice;Frenette, Jerome
Dumont N，Bouchard P，Frenette J.中性粒细胞诱导的骨骼肌损伤：后肢卸载和重新加载后的计算和控制的反应。Am J Physiol Regul Integr Comp Physiol 295：R1831-R1838,2008.2008年9月10日首次出版；DOI：10.1152/ajpregu.90318.2008-中性粒细胞吞噬细胞坏死碎片并释放细胞因子、酶和氧化因子。在本研究中，我们使用卸载和重新加载模型研究了中性粒细胞在肌肉损伤、功能障碍和恢复中的作用。小鼠接受10天的后肢卸载，在重新加载之前，用抗Ly6G/Ly6C抗体瞬时耗尽中性粒细胞。用免疫组织化学和功能学方法检测白细胞聚集和肌肉功能。此外，将卸载和重新加载的比目鱼肌与脂多糖(100 mU g/ml)体外孵育，以确定外源性刺激是否会激活中性粒细胞反应而产生广泛的肌肉损伤。每小时记录一次收缩特性，持续6小时，然后将肌肉孵育在橘子中以评估肌肉损伤。在萎缩和重新加载的比目鱼肌中，中性粒细胞的消耗既不影响肌力的丧失，也不影响恢复的时间。然而，与中性粒细胞耗尽的萎缩和重新加载的比目鱼肌相比，含有高浓度中性粒细胞的萎缩和重新加载的比目鱼肌在体外与脂多糖孵育后的力量损失要大20%。Procion橙色染料还证实，在脂多糖存在的情况下，中性粒细胞导致肌膜损伤增加2.5倍。这些结果表明，在改良的机械负荷过程中，中性粒细胞的渗透得到了高度的调节和有效的消除，除非中性粒细胞的激活状态被脂多糖的存在改变，否则不会对肌纤维造成明显的损伤。
Dumont N, Bouchard P, Frenette J. Neutrophil-induced skeletal muscle damage: a calculated and controlled response following hindlimb unloading and reloading. Am J Physiol Regul Integr Comp Physiol 295: R1831-R1838, 2008. First published September 10, 2008; doi:10.1152/ajpregu.90318.2008.-Neutrophils phagocyte necrotic debris and release cytokines, enzymes, and oxidative factors. In the present study, we investigated the contribution of neutrophils to muscle injury, dysfunction, and recovery using an unloading and reloading model. Mice were submitted to 10 days of hindlimb unloading and were transiently depleted in neutrophils with anti-Ly6G/Ly6C antibody prior to reloading. Leukocyte accumulation and muscle function were assessed immunohistologically and functionally in vitro. In addition, soleus muscles submitted to unloading and reloading were incubated in vitro with LPS ( 100 mu g/ml) to determine whether exogenous stimulus would activate neutrophil response and produce extensive muscle damage. Contractile properties were recorded every hour for 6 h, and muscles were subsequently incubated in procion orange to assess muscle damage. Neutrophil depletion affected neither the loss in muscle force nor the time of recovery in atrophied and reloaded soleus muscles. However, atrophied and reloaded soleus muscles that contained high concentration of neutrophils experienced a 20% greater loss in force than atrophied and reloaded soleus muscles depleted in neutrophils following in vitro incubation with LPS. Procion orange dye also confirmed that neutrophils induced a 2.5-fold increase in muscle membrane damage in the presence of LPS. These results show that neutrophil infiltration during modified mechanical loading is highly regulated and efficiently eliminated, with no significant muscle fiber injury unless the activation state of neutrophils is modified by the presence of LPS.