在小鼠中，中性粒细胞会导致肌肉损伤，并在延长收缩后阻碍其恢复。
Neutrophils contribute to muscle injury and impair its resolution after lengthening contractions in mice.
作者信息
Pizza Francis X, Peterson Jennifer M, Baas Joel H, Koh Timothy J
机构信息
Dept of Kinesiology, The University of Toledo, 2801 W. Bancroft Street, Toledo, OH 43606, USA.
出版信息
J Physiol. 2005 Feb 1;562(Pt 3):899-913. doi: 10.1113/jphysiol.2004.073965. Epub 2004 Nov 18.
We tested the hypotheses that: (1) neutrophil accumulation after contraction-induced muscle injury is dependent on the beta(2) integrin CD18, (2) neutrophils contribute to muscle injury and oxidative damage after contraction-induced muscle injury, and (3) neutrophils aid the resolution of contraction-induced muscle injury. These hypotheses were tested by exposing extensor digitorum longus (EDL) muscles of mice deficient in CD18 (CD18(-/-); Itgb2(tm1Bay)) and of wild type mice (C57BL/6) to in situ lengthening contractions and by quantifying markers of muscle inflammation, injury, oxidative damage and regeneration/repair. Neutrophil concentrations were significantly elevated in wild type mice at 6 h and 3 days post-lengthening contractions; however, neutrophils remained at control levels at these time points in CD18-/- mice. These data indicate that CD18 is required for neutrophil accumulation after contraction-induced muscle injury. Histological and functional (isometric force deficit) signs of muscle injury and total carbonyl content, a marker of oxidative damage, were significantly higher in wild type relative to CD18-/- mice 3 days after lengthening contractions. These data show that neutrophils exacerbate contraction-induced muscle injury. After statistically controlling for differences in the force deficit at 3 days, wild type mice also demonstrated a higher force deficit at 7 days, a lower percentage of myofibres expressing embryonic myosin heavy chain at 3 and 7 days, and a smaller cross sectional area of central nucleated myofibres at 14 days relative to CD18-/- mice. These observations suggest that neutrophils impair the restoration of muscle structure and function after injury. In conclusion, neutrophil accumulation after contraction-induced muscle injury is dependent on CD18. Furthermore, neutrophils appear to contribute to muscle injury and impair some of the events associated with the resolution of contraction-induced muscle injury.
我们检验了以下假设
（1）收缩诱导的肌肉损伤后中性粒细胞的积聚依赖于β₂整合素CD18；（2）中性粒细胞在收缩诱导的肌肉损伤后会导致肌肉损伤和氧化损伤；（3）中性粒细胞有助于收缩诱导的肌肉损伤的恢复。通过对缺乏CD18的小鼠（CD18⁻/⁻；Itgb2ᵗᵐ¹ᴮᵃʸ）和野生型小鼠（C57BL/6）的趾长伸肌（EDL）进行原位延长收缩，并对肌肉炎症、损伤、氧化损伤和再生/修复的标志物进行定量，来检验这些假设。在延长收缩后6小时和3天，野生型小鼠的中性粒细胞浓度显著升高；然而，在这些时间点，CD18⁻/⁻小鼠的中性粒细胞水平仍维持在对照水平。这些数据表明，收缩诱导的肌肉损伤后中性粒细胞的积聚需要CD18。延长收缩3天后，与CD18⁻/⁻小鼠相比，野生型小鼠的肌肉损伤的组织学和功能（等长力缺失）迹象以及氧化损伤标志物总羰基含量显著更高。这些数据表明中性粒细胞会加剧收缩诱导的肌肉损伤。在对3天时力缺失的差异进行统计学控制后，与CD18⁻/⁻小鼠相比，野生型小鼠在7天时也表现出更高的力缺失，在3天和7天时表达胚胎型肌球蛋白重链的肌纤维百分比更低，在14天时中央有核肌纤维的横截面积更小。这些观察结果表明中性粒细胞会损害损伤后肌肉结构和功能的恢复。总之，收缩诱导的肌肉损伤后中性粒细胞的积聚依赖于CD18。此外，中性粒细胞似乎会导致肌肉损伤，并损害一些与收缩诱导的肌肉损伤恢复相关的事件。
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