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MCP‐1 deficiency causes altered inflammation with impaired skeletal muscle regeneration
Author(s) -
Shireman Paula K.,
ContrerasShan Verónica,
Ochoa Oscar,
Karia Bijal P.,
Michalek Joel E.,
McManus Linda M.
Publication year - 2007
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0506356
Subject(s) - inflammation , skeletal muscle , biology , chemokine , regeneration (biology) , endocrinology , medicine , myeloperoxidase , macrophage , immunology , in vitro , microbiology and biotechnology , biochemistry
We examined the role of MCP‐1, a potent chemotactic and activating factor for macrophages, in perfusion, inflammation, and skeletal muscle regeneration post‐ischemic injury. MCP‐1−/− or C57Bl/6J control mice [wild‐type (WT)] underwent femoral artery excision (FAE). Muscles were collected for histology, assessment of tissue chemokines, and activity measurements of lactate dehydrogenase (LDH) and myeloperoxidase. In MCP‐1−/− mice, restoration of perfusion was delayed, and LDH and fiber size, indicators of muscle regeneration, were decreased. Altered inflammation was observed with increased neutrophil accumulation in MCP‐1−/− versus WT mice at Days 1 and 3 ( P ≤0.003), whereas fewer macrophages were present in MCP‐1−/− mice at Day 3. As necrotic tissue was removed in WT mice, macrophages decreased (Day 7). In contrast, macrophage accumulation in MCP‐1−/− was increased in association with residual necrotic tissue and impaired muscle regeneration. Consistent with altered inflammation, neutrophil chemotactic factors (keratinocyte‐derived chemokine and macrophage inflammatory protein‐2) were increased at Day 1 post‐FAE. The macrophage chemotactic factor MCP‐5 was increased significantly in WT mice at Day 3 compared with MCP‐1−/− mice. However, at post‐FAE Day 7, MCP‐5 was significantly elevated in MCP‐1−/− mice versus WT mice. Addition of exogenous MCP‐1 did not induce proliferation in murine myoblasts (C2C12 cells) in vitro. MCP‐1 is essential for reperfusion and the successful completion of normal skeletal muscle regeneration after ischemic tissue injury. Impaired muscle regeneration in MCP‐1−/− mice suggests an important role for macrophages and MCP‐1 in tissue reparative processes.