Macrophages recruited via CCR2 produce insulin-like growth factor-1 to repair acute skeletal muscle injury

Haiyan Lu, Danping Huang, Noah Saederup, Israel F. Charo, Richard M. Ransohoff, Lan Zhou

Research output: Contribution to journalArticlepeer-review

159 Scopus citations

Abstract

CC chemokine receptor 2 (CCR2) is essential to acute skeletal muscle injury repair. We studied the subpopulation of inflammatory cells recruited via CCR2 signaling and their cellular functions with respect to muscle regeneration. Mobilization of monocytes/macrophages (MOs/MPs), but not lymphocytes or neutrophils, was impaired from bone marrow to blood and from blood to injured muscle in Ccr2-/- mice. While the Ly-6C+ but not the Ly-6C- subset of MOs/MPs was significantly reduced in blood, both subsets were drastically reduced in injured muscle of Ccr2-/- mice. Expression of insulin-like growth factor-1 (IGF-I) was markedly up-regulated in injured muscle of wild-type but not Ccr2-/- mice. IGF-I was strongly expressed by macrophages within injured muscle, more prominently by the Ly-6C- subset. A single injection of IGF-I, but not PBS, into injured muscle to replace IGF-I remarkably improved muscle regeneration in Ccr2 -/- mice. CCR2 was not detected in myogenic cells or capillary endothelial cells in injured muscle to suggest its direct involvement in muscle regeneration or angiogenesis. We conclude that CCR2 is essential to acute skeletal muscle injury repair primarily by recruiting Ly-6C+ MOs/MPs. Within injured muscle, these cells conduct phagocytosis, contribute to accumulation of intramuscular Ly-6C- macrophages, and produce a high level of IGF-I to promote muscle regeneration.

Original languageEnglish (US)
Pages (from-to)358-369
Number of pages12
JournalFASEB Journal
Volume25
Issue number1
DOIs
StatePublished - Jan 2011

Keywords

  • Chemokine
  • Chemokine receptor
  • IGF-I
  • Inflammation
  • Skeletal muscle regeneration

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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