Hypoxia: how does the monocyte-macrophage system respond to changes in oxygen availability?

Abstract

Hypoxia is an important feature of inflamed tissue, such as the RA joint. Activated monocytes/macrophages and endothelial cells play a pivotal role in the pathogenesis of RA, implicated in the mechanism of inflammation and erosion. During development, myeloid progenitor cells sequentially give rise to monoblasts, promonocytes, and monocytes that are released from the bone marrow into the bloodstream. After extravasation, monocytes differentiate into long-lived, tissue-specific macrophages or DCs. The effect of different oxygen concentrations experienced by these cells during maturation represents a novel aspect of this developmental process. In inflamed joint tissue, the microvascular architecture is highly dysregulated; thus, efficiency of oxygen supply to the synovium is poor. Therefore, invading cells must adapt instantaneously to changes in the oxygen level of the microenvironment. Angiogenesis is an early event in the inflammatory joint, which is important in enabling activated monocytes to enter via endothelial cells by active recruitment to expand the synovium into a "pannus", resulting in cartilage degradation and bone destruction. The increased metabolic turnover of the expanding synovial pannus outpaces the dysfunctional vascular supply, resulting in hypoxia. The abnormal bioenergetics of the microenvironment further promotes synovial cell invasiveness. In RA, joint hypoxia represents a potential threat to cell function and survival. Notably, oxygen availability is a crucial parameter in the cellular energy metabolism, itself an important factor in determining the function of immune cells.

Effects of PVA coated nanoparticles on human immune cells

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“…In general, monocytes are patrolling cells within the bloodstream that recognize pathogens or respond to inflammatory stimuli. 69 Once activated, a differentiation process is initiated that leads to the development of macrophages. These cells primarily ingest the pathogens for rapid killing and elimination and further regulate inflammatory reactions by producing proinflammatory or anti-inflammatory cytokines.…”

Lack of the Transcription Factor Hypoxia-Inducible Factor 1α (HIF-1α) in Macrophages Accelerates the Necrosis of Mycobacterium avium-Induced Granulomas

“…Therefore, it is possible that the centers of large granulomas become hypoxic due to this reduction in blood supply, leading to the death of the cells further away from the blood vessels, i.e., macrophages within the deep core of the granuloma. However, it is known that macrophages can adapt to low-oxygen tensions found in inflammatory sites (49,50). This adaptation, as in most cells, involves the regulation of metabolic pathways controlled by the HIF system.…”

Differential Regulation of Macrophage Glucose Metabolism by Macrophage Colony-stimulating Factor and Granulocyte-Macrophage Colony-stimulating Factor: Implications for 18F FDG PET Imaging of Vessel Wall Inflammation

“…Monocytes and macrophages use diverse metabolic pathways to adapt to various microenvironments, which range from well-oxygenated tissues and blood to inflamed and often hypoxic tissues (27). Macrophages have the capacity to effectively switch to glycolysis after exposure to hypoxia (14,17), bacterial products (9,13), or in response to certain other proinflammatory stimuli (eg, modified lipoproteins) (12,15).…”