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J Clin Invest. 2005 Jul;115(7):1806-15.

HIF-1alpha expression regulates the bactericidal capacity of phagocytes.

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  • 1Division of Biological Sciences, Department of Pediatrics, University of California, San Diego, La Jolla, CA, USA.

Abstract

Hypoxia is a characteristic feature of the tissue microenvironment during bacterial infection. Here we report on our use of conditional gene targeting to examine the contribution of hypoxia-inducible factor 1, alpha subunit (HIF-1alpha) to myeloid cell innate immune function. HIF-1alpha was induced by bacterial infection, even under normoxia, and regulated the production of key immune effector molecules, including granule proteases, antimicrobial peptides, nitric oxide, and TNF-alpha. Mice lacking HIF-1alpha in their myeloid cell lineage showed decreased bactericidal activity and failed to restrict systemic spread of infection from an initial tissue focus. Conversely, activation of the HIF-1alpha pathway through deletion of von Hippel-Lindau tumor-suppressor protein or pharmacologic inducers supported myeloid cell production of defense factors and improved bactericidal capacity. HIF-1alpha control of myeloid cell activity in infected tissues could represent a novel therapeutic target for enhancing host defense.

Comment in

PMID:
16007254
[PubMed - indexed for MEDLINE]
PMCID:
PMC1159132
Free PMC Article

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