Functional alterations in macrophages after hypoxia selection.
Regions of low oxygen tension are common features of inflamed and infected tissues and provide physiologic selective pressure for the expansion of cells with enhanced hypoxia tolerance. The aim of this study was to investigate whether macrophages resistant to death induced by hypoxia were accompanied by functional alterations. A mouse macrophage cell line (J774 cells) was used to obtain subpopulations of death-resistant macrophages induced by long-term exposure to severe hypoxia (<1% O(2)). The results indicated that exposing J774 macrophages to periods of severe hypoxia results in the selection of cells with phenotypes associated with the modulation of heat-shock protein 70 kDa (HSP70) expression, tumor necrosis factor-alpha (TNF-alpha), and nitric oxide (NO) production and reduced susceptibility to parasite Leishmania infection. Thus, we suggest that hypoxia-selected macrophages may influence the outcome of inflammation and infection.
Degrossoli
Adriana
A
Department of Parasitology, Biology Institute, Universidade Estadual de Campinas, Caixa Postal 6109, Cep 13083-970, Campinas, São Paulo, Brazil.
Giorgio
Selma
S
D000220:Adaptation, Biological; D000818:Animals; D015153:Blotting, Western; D015687:Cell Hypoxia; D002460:Cell Line; D050884:HSP72 Heat-Shock Proteins / Q000096:biosynthesis; D007891:Leishmania / Q000502:physiology*; D008264:Macrophages / Q000469:parasitology* / Q000502:physiology*; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D050884:HSP72 Heat-Shock Proteins; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide