Selective deficiency of HIF-1alpha in myeloid cells influences secondary intention wound healing in mouse skin

In Vivo. 2009 Nov-Dec;23(6):879-84.


Background: Hypoxia-inducible factor-1 (HIF-1) influences myeloid cell function. In this study we examined the role of myeloid cell HIF-1alpha on wound healing in vivo using a cell-specific knockout (KO) mouse model.

Materials and methods: HIF-1alpha KO mice and wild-type (WT) controls received 8 mm full thickness dorsal dermal wounds. Wound dimensions were measured until full closure. Tissue was obtained from 3-day-old wounds for (immuno-)histochemical analysis. Production of interleukin-1beta (IL-1beta) and nitric oxide (NO) in response to lipopolysaccharide (LPS) and/or desferrioxamine (DFX) was examined in vitro.

Results: Early wound closure occurred significantly faster in HIF-1alpha KO mice than in WT mice. Wounds of KO mice contained similar numbers of neutrophils and macrophages, but more activated keratinocytes, consistent with accelerated re-epithelialization. Interestingly, while LPS and LPS+DFX elicited a similar IL-1beta response in macrophages from the 2 mouse types, NO production was blunted in HIF-1alpha KO macrophages.

Conclusion: Absence of HIF-1alpha in myeloid cells accelerates the early phase of secondary intention wound healing in vivo. This may be associated with a deficient ability of myeloid cells to initiate an appropriate NO production response. Pharmacologic modulators of HIF-1alpha should be explored in situations with abnormal wound healing.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cells, Cultured
  • Deferoxamine / pharmacology
  • Drug Combinations
  • Female
  • Hypoxia-Inducible Factor 1, alpha Subunit / deficiency*
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Interleukin-1beta / metabolism
  • Keratinocytes / metabolism
  • Keratinocytes / pathology
  • Lipopolysaccharides / pharmacology
  • Macrophages / drug effects
  • Macrophages / metabolism*
  • Macrophages / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nitric Oxide / metabolism
  • Skin / injuries
  • Skin / metabolism*
  • Skin / pathology
  • Wound Healing / drug effects
  • Wound Healing / physiology*


  • Drug Combinations
  • Hif1a protein, mouse
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Interleukin-1beta
  • Lipopolysaccharides
  • Nitric Oxide
  • Deferoxamine