Adaptations of Energy Metabolism in the Cultivated Macrophage

Simon, Lawrence M.; Axline, Stanton G.; Horn, Barry R.; Robin, Eugene D.

doi:10.1084/jem.138.6.1413

Cited by 28 publications

(15 citation statements)

References 19 publications

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“…Similar observations were made in endothelial cells, which are tolerant to hypoxia and which reduce HSP70 to levels observed under low oxygen tension [27]. Endothelial cells as well as macrophages are, in contrast to most other mammalian cell types, well adapted to low oxygen levels by changing their metabolism to anaerobiosis glycolysis [8,19,32]. Thus, we may assume that these cells are not stressed by this condition, which may be the reason why they do not stimulate HSP70 in response to hypoxia.…”

Section: Discussionsupporting

confidence: 59%

Hypoxia Modulates Expression of the 70-kD Heat Shock Protein and Reduces <i>Leishmania</i> Infection in Macrophages

Degrossoli¹,

Colhone²,

Arrais-Silva³

et al. 2004

J Biomed Sci

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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.

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Section: Discussionsupporting

confidence: 59%

Hypoxia Modulates Expression of the 70-kD Heat Shock Protein and Reduces <i>Leishmania</i> Infection in Macrophages

Degrossoli¹,

Colhone²,

Arrais-Silva³

et al. 2004

J Biomed Sci

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“…This increase in PyKi and PFK, under hypoxic conditions, may in turn be related to another more general mechanism. We have shown that changes in energy metabolism enzyme activities (both glycolytic and those of oxidative phosphorylation) are regulated by 02 tension in alveolar and peritoneal macrophages (13,31). The present studies demonstrate the operation of this adaptive mechanism in another cell type.…”

Section: Discussionmentioning

confidence: 55%

Bioenergetic Pattern of Isolated Type II Pneumocytes in Air and during Hypoxia

Simon¹,

Robin²,

Raffin³

et al. 1978

J. Clin. Invest.

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A B S T R A C T The bioenergetic pattern of a cell clone derived from rat lung with ultrastructural and biochemical characteristics like those of type II pneumocytes (T-II-P), has been studied in a tissue culture system. During air cultivation, these cells have a high rate of aerobic and anaerobic glycolysis associated with high activities of two rate-limiting enzymes in glycolysis (pyruvate kinase [PyKi] and phosphofructokinase [PFK]). This is present despite the rates of oxygen consumption and activities of cytochrome oxidase (CyOx) similar to other lung cells. Presumably the high rate of aerobic glycolysis explains the substantial lactate production previously described in lung slices and in the intact perfused lung.Hypoxic cultivation results in a decrease in CyOx. Acute re-exposure to air does not restore the oxygen consumption to normal, presumably as a result of de-creased mitochondrial 02 utilization associated with decreased CyOx activity. As a result, hypoxically cultivated T-II-P cells have a decreased capacity for mitochondrial ATP generation in air as compared to air-cultivated cells. During hypoxia, aerobic and anaerobic glycolysis are further increased as well as the activities of PyKi and PFK.The high rate of glycolysis and high activities of PyKi and PFK in cultivated T-II-P appear to reflect intrinsic genetic regulation. The decreased CyOx activity and increased PyKi and PFK activities in hypoxic T-II-P appear to reflect alterations in enzyme biosynthesis/biodegradation regulated by 02 availability.

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“…3C); also, we found that the Akt inhibitor Akt VIII (10 M) did not inhibit the hypoxia-stimulated BMM survival in the absence of CSF-1 over a 48-h period (data not shown). The downregulation by hypoxia of the antiapoptotic Bcl-2 and Bcl-x L proteins, in both CSF-1-depleted and cycling BMM, is perhaps surprising given the literature on other cells (21) but could be due to suppression of overall protein synthesis reported during hypoxia for macrophages (50) and other cell types (51); consistent with this possibility, we found that mRNA levels of the two antiapoptotic proteins did not parallel the loss of protein (data not shown). In any case, Bcl-2 and Bcl-x L expression did not correlate with enhanced macrophage survival for CSF-1-depleted BMM; also, cycling BMM, that is, in the presence of a high CSF-1 concentration, whose survival is not modulated by hypoxia, also showed the same reduction.…”

Section: Discussionmentioning

confidence: 85%

Hypoxia Prolongs Monocyte/Macrophage Survival and Enhanced Glycolysis Is Associated with Their Maturation under Aerobic Conditions

Roiniotis

Dinh

Masendycz

et al. 2009

The Journal of Immunology

150

124

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In chronic inflammatory lesions macrophages are abundant and adapt to the low oxygen concentrations often present there. In low oxygen some cell types die by apoptosis, as reported for macrophage cell lines, while others survive better as they shift their metabolism to anaerobic glycolysis. It was found here that hypoxia prolongs the survival of murine bone marrow-derived macrophages, either in the absence or presence of low CSF-1 (M-CSF) concentrations. Although Akt activity increased in bone marrow-derived macrophages in the low oxygen conditions, the levels of both anti- and proapoptotic Bcl-2 family members decreased. Glycolysis was enhanced as judged by increased glucose uptake, glucose transporter expression, lactate dehydrogenase mRNA expression, and lactate secretion. Human monocytes responded similarly to low oxygen, and a number of genes associated with glycolysis were shown by microarray analysis and quantitative PCR to be up-regulated. Interestingly, human monocyte-derived macrophages showed evidence of enhanced glycolysis even under aerobic conditions. It is proposed that certain monocyte/macrophage populations survive better under conditions of low oxygen, thereby contributing to their increased numbers at sites of chronic inflammation and tumors; it is also proposed that as macrophages differentiate from monocytes they begin to adopt a glycolytic metabolism allowing them to adapt readily when exposed to low oxygen conditions.

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Adaptations of Energy Metabolism in the Cultivated Macrophage

Cited by 28 publications

References 19 publications

Hypoxia Modulates Expression of the 70-kD Heat Shock Protein and Reduces <i>Leishmania</i> Infection in Macrophages

Hypoxia Modulates Expression of the 70-kD Heat Shock Protein and Reduces <i>Leishmania</i> Infection in Macrophages

Bioenergetic Pattern of Isolated Type II Pneumocytes in Air and during Hypoxia

Hypoxia Prolongs Monocyte/Macrophage Survival and Enhanced Glycolysis Is Associated with Their Maturation under Aerobic Conditions

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