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Department of Parasitology, Biology Institute, Universidade Estadual de Campinas, Campinas 13083-970, São Paulo, Brazil
To whom requests for reprints should be addressed at 1 Department of Parasitology, Biology Institute, Universidade Estadual de Campinas, Caixa Postal 6109, Cep 13083-970, Campinas, São Paulo, Brazil. E-mail: sgiorgio{at}unicamp.br
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% O2). 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-
(TNF-
), 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. Exp Biol Med 232:8895, 2007
Key Words: hypoxia selection macrophages inflammatory responses Leishmania
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