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Hypoxia causes an increase in phagocytosis by macrophages in a HIF-1α-dependent manner
- Source :
- Journal of Leukocyte Biology. 82:1257-1265
- Publication Year :
- 2007
- Publisher :
- Oxford University Press (OUP), 2007.
-
Abstract
- Phagocytosis is the process by which microbial pathogens are engulfed by macrophages and neutrophils and represents the first line of defense against bacterial infection. The importance of phagocytosis for bacterial clearance is of particular relevance to systemic inflammatory diseases, which are associated with the development of hypoxia, yet the precise effects of hypoxia on phagocytosis remain largely unexplored. We now hypothesize that hypoxia inhibits phagocytosis in macrophages and sought to determine the mechanisms involved. Despite our initial prediction, hypoxia significantly increased the phagocytosis rate of particles in vitro by RAW264.7 and primary peritoneal macrophages and increased phagocytosis of labeled bacteria in vivo by hypoxic mice compared with normoxic controls. In understanding the mechanisms involved, hypoxia caused no changes in RhoA-GTPase signaling but increased the phosphorylation of p38-MAPK significantly. Inhibition of p38 reversed the effects of hypoxia on phagocytosis, suggesting a role for p38 in the hypoxic regulation of phagocytosis. Hypoxia also significantly increased the expression of hypoxia-inducible factor-1α (HIF-1α) in macrophages, which was reversed after p38 inhibition, suggesting a link between p38 activation and HIF-1α expression. It is striking that small interfering RNA knockdown of HIF-1α reversed the effects of hypoxia on phagocytosis, and overexpression of HIF-1α caused a surprising increase in phagocytosis compared with nontransfected controls, demonstrating a specific role for HIF-1α in the regulation of phagocytosis. These data indicate that hypoxia enhances phagocytosis in macrophages in a HIF-1α-dependent manner and shed light on an important role for HIF-1α in host defense.
- Subjects :
- Small interfering RNA
p38 mitogen-activated protein kinases
Phagocytosis
Immunology
Apoptosis
Biology
p38 Mitogen-Activated Protein Kinases
Mice
In vivo
Escherichia coli
medicine
Animals
Humans
Immunology and Allergy
Phosphorylation
RNA, Small Interfering
Hypoxia
Cells, Cultured
Mice, Inbred C3H
Gene knockdown
Tumor Necrosis Factor-alpha
Cell Differentiation
Cell Biology
Hypoxia (medical)
Hypoxia-Inducible Factor 1, alpha Subunit
Cell biology
Gene Expression Regulation
Macrophages, Peritoneal
Tumor necrosis factor alpha
medicine.symptom
rhoA GTP-Binding Protein
Subjects
Details
- ISSN :
- 19383673 and 07415400
- Volume :
- 82
- Database :
- OpenAIRE
- Journal :
- Journal of Leukocyte Biology
- Accession number :
- edsair.doi.dedup.....826dc33f98e08a19d1f9931ba8a1917d