Monocyte-derived macrophages matured under prolonged hypoxia transcriptionally up-regulate HIF-1? mRNA
Monocyte-derived macrophages matured under prolonged hypoxia transcriptionally up-regulate HIF-1? mRNA
This study tested the hypothesis that prolonged severe hypoxia during monocyte to macrophage differentiation results in macrophages with a pattern of gene expression and phenotype distinct from those maturing in normal oxygen levels. Macrophages accumulate in hypoxic and anoxic areas within pathological sites such as tumours, wounds, and arthritic joints, and have been proposed as vehicles for gene therapy delivery to such tissues. Several non-pathological tissues are also hypoxic. We therefore argue that differentiation from monocyte to macrophage in hypoxic conditions is a common occurrence. However, the effect of long term severe hypoxia on monocyte to macrophage differentiation has not been studied. Here, using primary human peripheral blood monocytes, we show that maturation for 5 days in 0.2% oxygen results in decreased phagocytosis, and decreased CD40 and CD206 expression. Chronic hypoxia induced much higher mRNA levels of the pro-angiogenic cytokine, VEGF, in adherence-purified macrophages (27-fold), CD14-magnetic bead purified monocytes (90-fold), and PBMC (104-fold) compared to acute (24h) hypoxia (11, 17 and 9-fold, respectively). This suggests that macrophages may play an even greater role in angiogenesis than previously appreciated. Furthermore, chronic hypoxia resulted in up-regulation of HIF-1? mRNA, in all monocyte-derived macrophage types studied. Actinomycin D experiments indicate that the increases in HIF-1? mRNA were not due to increased mRNA stability. To our knowledge this is the first study demonstrating up-regulation of HIF-1? mRNA by hypoxia in macrophages. Taken together, the data support the hypothesis that hypoxia affects monocyte to macrophage maturation, resulting in a distinct gene expression pattern and phenotype.
Staples, Karl J.
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Sotoodehnejadnematalahi, Fattah
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Pearson, Helen
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Frankenberger, Marion
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Francescut, Lorenza
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Ziegler-Heitbrock, Loems
71bb9dd4-262c-46ba-9c10-1be5941ffca4
Burke, Bernard
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22 December 2010
Staples, Karl J.
e0e9d80f-0aed-435f-bd75-0c8818491fee
Sotoodehnejadnematalahi, Fattah
5913f7a4-4490-43a1-9829-58364cfcd958
Pearson, Helen
5949c937-ba10-4ff2-9f15-8c60c7b7460f
Frankenberger, Marion
55dd9ff6-ea3a-479c-a105-2d4fe5cd81ce
Francescut, Lorenza
022f1fbc-78f7-4386-b0b0-8f04275bcee9
Ziegler-Heitbrock, Loems
71bb9dd4-262c-46ba-9c10-1be5941ffca4
Burke, Bernard
cff79772-daee-4227-9002-3ad729923d17
Staples, Karl J., Sotoodehnejadnematalahi, Fattah, Pearson, Helen, Frankenberger, Marion, Francescut, Lorenza, Ziegler-Heitbrock, Loems and Burke, Bernard
(2010)
Monocyte-derived macrophages matured under prolonged hypoxia transcriptionally up-regulate HIF-1? mRNA.
Immunobiology.
(doi:10.1016/j.imbio.2010.12.005).
(PMID:21281980)
Abstract
This study tested the hypothesis that prolonged severe hypoxia during monocyte to macrophage differentiation results in macrophages with a pattern of gene expression and phenotype distinct from those maturing in normal oxygen levels. Macrophages accumulate in hypoxic and anoxic areas within pathological sites such as tumours, wounds, and arthritic joints, and have been proposed as vehicles for gene therapy delivery to such tissues. Several non-pathological tissues are also hypoxic. We therefore argue that differentiation from monocyte to macrophage in hypoxic conditions is a common occurrence. However, the effect of long term severe hypoxia on monocyte to macrophage differentiation has not been studied. Here, using primary human peripheral blood monocytes, we show that maturation for 5 days in 0.2% oxygen results in decreased phagocytosis, and decreased CD40 and CD206 expression. Chronic hypoxia induced much higher mRNA levels of the pro-angiogenic cytokine, VEGF, in adherence-purified macrophages (27-fold), CD14-magnetic bead purified monocytes (90-fold), and PBMC (104-fold) compared to acute (24h) hypoxia (11, 17 and 9-fold, respectively). This suggests that macrophages may play an even greater role in angiogenesis than previously appreciated. Furthermore, chronic hypoxia resulted in up-regulation of HIF-1? mRNA, in all monocyte-derived macrophage types studied. Actinomycin D experiments indicate that the increases in HIF-1? mRNA were not due to increased mRNA stability. To our knowledge this is the first study demonstrating up-regulation of HIF-1? mRNA by hypoxia in macrophages. Taken together, the data support the hypothesis that hypoxia affects monocyte to macrophage maturation, resulting in a distinct gene expression pattern and phenotype.
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Published date: 22 December 2010
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Local EPrints ID: 185851
URI: http://eprints.soton.ac.uk/id/eprint/185851
ISSN: 0171-2985
PURE UUID: 04793d28-8aab-4b31-ab24-e1fb238f22b4
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Date deposited: 11 May 2011 10:44
Last modified: 15 Mar 2024 03:27
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Author:
Fattah Sotoodehnejadnematalahi
Author:
Helen Pearson
Author:
Marion Frankenberger
Author:
Lorenza Francescut
Author:
Loems Ziegler-Heitbrock
Author:
Bernard Burke
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