title: Hypoxia modulates expression of the 70-kD heat shock protein and reduces Leishmania infection in macrophages.
abstract: Hypoxia, a microenvironmental factor present in diseased tissues, has been recognized as a specific metabolic stimulus or a signal of cellular response. Experimental hypoxia has been reported to induce adaptation in macrophages such as differential migration, elevation of proinflammatory cytokines and glycolytic enzyme activities, and decreased phagocytosis of inert particles. In this study we demonstrate that although exposure to hypoxia (5% O2, 5% CO2, and balanced N2) did not change macrophage viability, or 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cleavage and proliferation, it significantly reduced expression of the 70-kD heat shock protein (HSP70), which was restored to prehypoxia levels after reoxygenation. The influence of low oxygen tension on macrophage functional activity was also studied, i.e. the ability of these cells to maintain or resist infection by a microorganism. We demonstrate that macrophages from two different sources (a murine cell line and primary cells) exposed to hypoxia were efficiently infected with Leishmania amazonensis, but after 24 h showed a reduction in the percentage of infected cells and of the number of intracellular parasites per macrophage, indicating that hypoxia induced macrophages to kill the intracellular parasites. These results support the notion that hypoxia, a microenvironmental factor, can modulate macrophage protein expression and functional activity.
authors.affiliation: Department of Parasitology, Biology Institute, Universidade Estadual de Campinas, Campinas, SP, Brazil.
authors.forename: Adriana
authors.initials: A
authors.lastname: Degrossoli
authors.forename: Marcelle Carolina
authors.initials: MC
authors.lastname: Colhone
authors.forename: Wagner Welber
authors.initials: WW
authors.lastname: Arrais-Silva
authors.forename: Selma
authors.initials: S
authors.lastname: Giorgio
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D002465:Cell Movement; D002470:Cell Survival; D004396:Coloring Agents / Q000494:pharmacology; D006019:Glycolysis; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis* / Q000737:chemistry; D000860:Hypoxia; D015151:Immunoblotting; D007891:Leishmania / Q000378:metabolism*; D007896:Leishmaniasis / Q000378:metabolism* / Q000517:prevention & control; D008264:Macrophages / Q000378:metabolism* / Q000469:parasitology*; D051379:Mice; D010100:Oxygen / Q000737:chemistry; D017382:Reactive Oxygen Species; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D013997:Time Factors
chemical_list: D004396:Coloring Agents; D018840:HSP70 Heat-Shock Proteins; D017382:Reactive Oxygen Species; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue; D010100:Oxygen