Shaping of monocyte and macrophage function by adenosine receptors

Abstract

Adenosine is an endogenous purine nucleoside that, following its release into the extracellular space, binds to specific adenosine receptors expressed on the cell surface. Adenosine appears in the extracellular space under metabolically stressful conditions, which are associated with ischemia, inflammation, and cell damage. There are 4 types of adenosine receptors (A 1 , A 2A , A 2B and A 3 ) and all adenosine receptors are members of the G protein-coupled family of receptors. Adenosine receptors are expressed on monocytes and macrophages and through these receptors adenosine modulates monocyte and macrophage function. Since monocytes and macrophages are activated by the same danger signals that cause accumulation of extracellular adenosine, adenosine receptors expressed on macrophages represent a sensor system that provide monocytes and macrophages with information about the stressful environment. Adenosine receptors, thus, allow monocytes and macrophages to fine-tune their responses to stressful stimuli. Here, we review the consequences of adenosine receptor activation on monocyte/macrophage function. We will detail the effect of stimulating the various adenosine receptor subtypes on macrophage differentiation/proliferation, phagocytosis, and tissue factor (TF) expression. We will also summarize our knowledge of how adenosine impacts the production of extracellular mediators secreted by monocytes and macrophages in response to toll-like receptor (TLR) ligands and other inflammatory stimuli. Specifically, we will delineate how adenosine affects the production of superoxide, nitric oxide (NO), tumor necrosis factor-α, interleukin (IL)-12, IL-10, and vascular endothelial growth factor (VEGF). A deeper insight into the regulation of monocyte and macrophage function by adenosine receptors should assist in developing new therapies for inflammatory diseases.

Heme Oxygenase-1 Contributes to an Alternative Macrophage Activation Profile Induced by Apoptotic Cell Supernatants

“…The rather marginal effect seen with CO and bilirubin in our experiments may open a further possibility that HO-1 translocates to the nucleus to bind to a transcription factor or a protein complex, resulting in enhanced transcription of Adora A 2A (Lin et al, 2007). Adora A 2A agonists are capable of not only blocking the inflammatory potential of human macrophages, such as pathogenstimulated NO, TNF-␣, or IL-12 production (Hasko et al, 2007) but also promoting wound healing in disease states such as diabetes (Montesinos et al, 1997).…”

Clearance of dying autophagic cells of different origin by professional and non-professional phagocytes

“…ADORA2A is a potent regulator of macrophage functions, including Fc receptor-mediated phagocytosis and pattern recognition receptor-mediated cytokine production. 39 Detailed studies are in progress in our laboratory to clarify the molecular mechanism and general implication of cytokine induction in macrophages.…”

The ecto-ATPDase CD39 is involved in the acquisition of the immunoregulatory phenotype by M-CSF-macrophages and ovarian cancer tumor-associated macrophages: Regulatory role of IL-27

“…These data suggested that the hydrolysis of ATP may be pivotal in regulating the immunoregulatory phenotype of M-CSF-macrophages. As macrophages express adenosine receptors and that adenosine receptor stimulation regulates IL-10 secretion, 51 we addressed the role of adenosine generated following ATP hydrolysis on the cellular fate of macrophages by using adenosine deaminase (ADA) that degrades adenosine, and caffeine that inhibits adenosine receptor. Results showed that inhibition of adenosine receptor during M-CSF-macrophages activation inhibits IL-10 secretion (Fig.…”