RANTES SECRETED FROM MACROPHAGES DISTURBS SKELETAL MUSCLE REGENERATION AFTER CARDIOTOXIN INJECTION IN Cbl-b-DEFICIENT MICE
RANTES SECRETED FROM MACROPHAGES DISTURBS SKELETAL MUSCLE REGENERATION AFTER CARDIOTOXIN INJECTION IN Cbl-b-DEFICIENT MICE
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DOI：
10.1002/mus.21829
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发表时间：
2011-02-01
期刊：
影响因子：
3.4
通讯作者：
Nikawa, Takeshi
中科院分区：
文献类型：
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作者：
Kohno, Shohei;Ueji, Tatsuya;Nikawa, Takeshi
Cbl-b 泛素连接酶基因的缺陷会激活小鼠的巨噬细胞。本研究旨在阐明巨噬细胞在 Cbl-b 缺陷小鼠肌肉变性/再生中的病理生理学作用。我们检查了 Cbl-b 缺陷小鼠注射心脏毒素的胫骨前肌中的免疫细胞浸润和细胞因子表达。与野生型小鼠相比，Cbl-b 基因表达的消除延迟了心脏毒素诱导的骨骼肌损伤的再生。在 Cbl-b 缺陷小鼠中注射心脏毒素后第 14 天，CD8 阳性 T 细胞仍然存在于受损肌肉中，但在野生型小鼠中，相同的细胞在这段时间内出现分散。 Cbl-b 缺陷小鼠的浸润巨噬细胞表现出 RANTES（激活调节，正常 T 细胞表达和分泌）的强烈表达，RANTES 是 CD8 阳性 T 细胞的趋化因子。反过来，针对 RANTES 的中和抗体显着抑制 CD8 阳性 T 细胞向肌肉的浸润，从而恢复受干扰的肌肉再生。 Cbl-b 是通过巨噬细胞中 RANTES 产生的细胞毒性 T 细胞浸润的重要调节因子。肌肉神经 43：223-229，2011
Deficiency of the Cbl-b ubiquitin ligase gene activates macrophages in mice. This study aimed to elucidate the pathophysiological roles of macrophages in muscle degeneration/regeneration in Cbl-b-deficient mice. We examined immune cell infiltration and cytokine expression in cardiotoxin-injected tibialis anterior muscle of Cbl-b-deficient mice. Ablation of the Cbl-b gene expression delayed regeneration of cardiotoxin-induced skeletal muscle damage compared with wild-type mice. CD8-positive T cells were still present in the damaged muscle on day 14 after cardiotoxin injection in Cbl-b-deficient mice, but there was dispersal of the same cells over that time-frame in wild-type mice. Infiltrating macrophages in Cbl-b-deficient mice showed strong expression of RANTES (regulated-on-activation, normal T cell expressed and secreted), a chemokine for CD8-positive T cells. In turn, a neutralizing antibody against RANTES significantly suppressed the infiltration of CD8-positive T cells into the muscle, resulting in restoration of the disturbed muscle regeneration. Cbl-b is an important regulatory factor for cytotoxic T-cell infiltration via RANTES production in macrophages. Muscle Nerve 43: 223-229, 2011