Dysregulation of monocyte/macrophage phenotype in wounds of diabetic mice

Cytokine. 2011 Nov;56(2):256-64. doi: 10.1016/j.cyto.2011.06.016. Epub 2011 Jul 30.


The hypothesis of this study was that cells of the monocyte/macrophage lineage (Mo/Mp) exhibit an impaired transition from pro-inflammatory to pro-healing phenotypes in wounds of diabetic mice, which contributes to deficient healing. Mo/Mp isolated from excisional wounds in non-diabetic db/+ mice exhibited a pro-inflammatory phenotype on day 5 post-injury, with high level expression of the pro-inflammatory molecules interleukin-1β, matrix metalloprotease-9 and inducible nitric oxide synthase. Wound Mo/Mp exhibited a less inflammatory phenotype on day 10 post-injury, with decreased expression of the pro-inflammatory molecules and increased expression of the alternative activation markers CD206 and CD36. In contrast, in db/db mice, the pro-inflammatory phenotype persisted through day 10 post-injury and was associated with reduced expression of insulin-like growth factor-1, transforming growth factor-β1 and vascular endothelial growth factor. Reduced levels of these growth factors in wounds of db/db mice may have contributed to impaired wound closure, reduced granulation tissue formation, angiogenesis and collagen deposition. The persistent pro-inflammatory wound Mo/Mp phenotype in db/db mice may have resulted from elevated levels of pro-inflammatory interleukin-1β and interferon-γ and reduced levels of anti-inflammatory interleukin-10 in the wound environment. Our findings are consistent with the hypothesis that dysregulation of Mo/Mp phenotypes contributes to impaired healing of diabetic wounds.

MeSH terms

  • Animals
  • Base Sequence
  • DNA Primers
  • Diabetes Mellitus, Experimental / immunology*
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Immunophenotyping*
  • Macrophages / immunology*
  • Mice
  • Monocytes / immunology*
  • Polymerase Chain Reaction
  • Wound Healing
  • Wounds and Injuries / immunology*


  • DNA Primers