Pharmacologic augmentation of hypoxia-inducible factor-1alpha with mimosine boosts the bactericidal capacity of phagocytes

J Infect Dis. 2008 Jan 15;197(2):214-7. doi: 10.1086/524843.

Abstract

Hypoxia-inducible factor (HIF)-1alpha is activated on exposure to bacterial pathogens and regulates the innate immune functions of phagocytes. We show here that the HIF-1alpha agonist mimosine can boost the capacity of human phagocytes and whole blood to kill the leading pathogen Staphylococcus aureus in a dose-dependent fashion and reduce the lesion size in a murine model of S. aureus skin infection. This provides the first proof of principle for a novel approach to the treatment of bacterial infection by pharmacologically augmenting the host phagocytic function.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Bactericidal Activity
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / agonists*
  • Hypoxia-Inducible Factor 1, alpha Subunit / immunology*
  • Immunity, Innate
  • Mice
  • Mice, Inbred C57BL
  • Mimosine / pharmacology*
  • Monocytes / immunology
  • Neutrophils / immunology
  • Phagocytes / immunology
  • Respiratory Burst
  • Staphylococcal Infections / drug therapy
  • Staphylococcal Infections / immunology
  • Staphylococcal Infections / microbiology
  • Staphylococcal Skin Infections / drug therapy*
  • Staphylococcal Skin Infections / immunology*
  • Staphylococcal Skin Infections / microbiology
  • Staphylococcus aureus / drug effects*
  • Staphylococcus aureus / pathogenicity
  • U937 Cells

Substances

  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Mimosine