MCP-1 deficiency causes altered inflammation with impaired skeletal muscle regeneration

Paula K. Shireman, Verónica Contreras-Shannon, Oscar Ochoa, Bijal P. Karia, Joel E. Michalek, Linda M. McManus

Research output: Contribution to journalArticlepeer-review

144 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)775-785
Number of pages11
JournalJournal of Leukocyte Biology
Volume81
Issue number3
DOIs
StatePublished - Mar 1 2007

Keywords

  • CCL2
  • Chemokines
  • Ischemia
  • Macrophage
  • Neutrophils

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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