DIFFERENTIAL RESPONSE OF MACROPHAGE SUBPOPULATIONS TO SOLEUS MUSCLE RELOADING AFTER RAT HINDLIMB SUSPENSION
DIFFERENTIAL RESPONSE OF MACROPHAGE SUBPOPULATIONS TO SOLEUS MUSCLE RELOADING AFTER RAT HINDLIMB SUSPENSION
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DOI：
10.1152/jappl.1994.77.1.290
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发表时间：
1994-07-01
影响因子：
3.3
通讯作者：
TIDBALL, JG
中科院分区：
文献类型：
--
作者：
STPIERRE, BA;TIDBALL, JG
在Wistar大鼠后肢悬吊10天后和恢复负重后2、4和7天的比目鱼肌中，研究了不同巨噬细胞群体与肌肉坏死和再生相关的假设。使用组织学特征（如肌纤维浸润）鉴定坏死，并使用发育肌球蛋白重链（dMHC）的免疫组织化学技术鉴定再生。光镜观察显示，重负荷2天的比目鱼肌中的坏死纤维被ED 1（+）和Ia（+）巨噬细胞侵入。再负荷2天的肌肉中侵入纤维的数量增加到2.8/mm（2），而年龄匹配的正常肌肉中为0.2/mm（2），但在恢复负重的第4天恢复到对照值。在恢复2天的肌肉间隙中，ED 1（+）和Ia（+）巨噬细胞的数量分别为369和332/mm（2），而对照比目鱼肌中分别为12和72/mm（2）。再加载7 d后，ED 1（+）细胞数与对照组相近。Ia（+）巨噬细胞在第4天减少到240/mm（2），但在7天后上升到高于对照值429/mm（2）。与对照组相比，在第4天和第7天重新加载的比目鱼肌中，间质空间中的ED 2（+）巨噬细胞增加了70-80%，但在任何时间点均未观察到坏死肌纤维浸润。使用单克隆抗dMHC抗体的免疫组织化学和免疫印迹显示，在重新加载4天和7天后，表达dMHC同种型的肌纤维的比例更大。这些发现表明，巨噬细胞亚群与后肢悬吊恢复过程中的不同阶段相关：ED 1（+）巨噬细胞与肌肉坏死相关，而ED 2（+）细胞与肌肉再生相关。这项研究的数据还表明，Ia（+）巨噬细胞可能对两个肌肉损伤反应阶段都有反应。
The hypothesis that distinct populations of macrophages are associated with muscle necrosis and regeneration was examined in Wistar rat soleus muscle after 10 days of hindlimb suspension and 2, 4, and 7 days after the resumption of weight bearing. Necrosis was identified using histological features, such as muscle fiber infiltration, and regeneration was identified using immunohistochemical techniques for developmental myosin heavy chain (dMHC). Light-microscopic observations show that necrotic fibers in 2-day reloaded soleus muscle were invaded by ED1(+) and Ia(+) macrophage. The number of invaded fibers in muscles reloaded for 2 days increased to 2.8/mm(2) compared with 0.2/mm(2) in age-matched normal muscle but returned to control values by the 4th day of resumed weight bearing. In the interstitial spaces of 2-day recovery muscle, ED1(+) and Ia(+) macrophages numbered 369 and 332/mm(2), respectively, compared with 12 and 72/mm(2), respectively, in control soleus. After 7 days of reloading, the number of ED1(+) cells was similar to that of control. Ia(+) macrophages decreased to 240/mm(2) at 4 days but after 7 days rose above control values to 429/mm(2) ED2(+) macrophages in 4- and 7-day reloaded soleus increased 70-80% in the interstitial spaces compared with control but were not observed to infiltrate necrotic muscle fibers at any time points. Immunohistochemistry and immunoblots using a monoclonal anti-dMHC antibody demonstrate a greater proportion of myofibers expressing dMHC isoforms after 4 and 7 days of reloading. These findings indicate that macrophage subpopulations are associated with distinct stages during the recovery process from hindlimb suspension: ED1(+) macrophages are associated with muscle necrosis, whereas ED2(+) cells are associated with muscle regeneration. Data from this investigation also suggest that Ia(+) macrophages may respond to both muscle injury response stages.