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Rantes secreted from macrophages disturbs skeletal muscle regeneration after cardiotoxin injection in Cbl‐b ‐deficient mice
Author(s) -
Kohno Shohei,
Ueji Tatsuya,
Abe Tomoki,
Nakao Reiko,
Hirasaka Katsuya,
Oarada Motoko,
HaradaSukeno Akiko,
Ohno Ayako,
Higashibata Akira,
Mukai Rie,
Terao Junji,
Okumura Yuushi,
Nikawa Takeshi
Publication year - 2011
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.21829
Subject(s) - cardiotoxin , skeletal muscle , chemokine , cd8 , biology , infiltration (hvac) , regeneration (biology) , microbiology and biotechnology , chemistry , immune system , immunology , endocrinology , physics , thermodynamics
Abstract 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, 2011