Adenosine A2a receptors induce heterologous desensitization of chemokine receptors

Zhang, Ning; Yang, De; Dong, Huifang; Chen, Qian; Dimitrova, Dessislava I.; Rogers, Thomas J.; Sitkovsky, Michail V.; Oppenheim, Joost J.

doi:10.1182/blood-2005-06-2599

Cited by 57 publications

(43 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Indeed, our data indicate that it is expressed at equal or even higher levels than the A 2A AR. Compared with recent reports using RT-PCR, the pattern of AR receptor expression in mouse bone marrow neutrophils seems to be similar to that of circulating human neutrophils, where A 2A -and A 3 AR expression is predominant, followed by low levels of expression of the A 2B AR subtype and little or no detectable expression of A 1 AR message Fortin et al, 2006;Zhang et al, 2006). Unlike the A 2A AR, expression of the A 3 AR was not increased in neutrophils obtained from mice treated with LPS, indicating that the A 3 AR may not be transcriptionally regulated by pro-inflammatory cytokines in neutrophils.…”

Section: Discussionsupporting

confidence: 47%

Activation of the A₃Adenosine Receptor Suppresses Superoxide Production and Chemotaxis of Mouse Bone Marrow Neutrophils

2008

View full text Add to dashboard Cite

show abstract

Section: Discussionsupporting

confidence: 47%

Activation of the A₃Adenosine Receptor Suppresses Superoxide Production and Chemotaxis of Mouse Bone Marrow Neutrophils

2008

View full text Add to dashboard Cite

show abstract

“…This is the first report demonstrating that adenosine can be released upon chemokine stimulation in the nervous system while the contrary event, e.g., adenosine-stimulated chemokine release, has been reported in mouse astrocytes for CCL2, which also exerts neuroprotective activity (42). In different cellular systems, functional cross-talk between adenosine and chemokine receptors has been described in terms of heterologous desensitization (43). Extracellular adenosine release is known to occur from both glial and neuronal cells (44).…”

Section: Discussionmentioning

confidence: 94%

Activity of Adenosine Receptors Type 1 Is Required for CX3CL1-Mediated Neuroprotection and Neuromodulation in Hippocampal Neurons

Lauro

Angelantonio

Cipriani

et al. 2008

The Journal of Immunology

102

View full text Add to dashboard Cite

The chemokine fractalkine (CX3CL1) is constitutively expressed by central neurons, regulating microglial responses including chemotaxis, activation, and toxicity. Through the activation of its own specific receptor, CX3CR1, CX3CL1 exerts both neuroprotection against glutamate (Glu) toxicity and neuromodulation of the glutamatergic synaptic transmission in hippocampal neurons. Using cultured hippocampal neuronal cell preparations, obtained from CX3CR1−/− (CX3CR1GFP/GFP) mice, we report that these same effects are mimicked by exposing neurons to a medium conditioned with CX3CL1-treated mouse microglial cell line BV2 (BV2-st medium). Furthermore, CX3CL1-induced neuroprotection from Glu toxicity is mediated through the adenosine receptor 1 (AR1), being blocked by neuronal cell preparations treatment with 1,3-dipropyl-8-cyclopentylxanthine (DPCPX), a specific inhibitor of AR1, and mimicked by both adenosine and the specific AR1 agonist 2-chloro-N6-cyclopentyladenosine. Similarly, experiments from whole-cell patch-clamped hippocampal neurons in culture, obtained from CX3CR1+/+ mice, show that CX3CL1-induced depression of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid- (AMPA-) type Glu receptor-mediated current (AMPA-current), is associated with AR1 activity being blocked by DPCPX and mimicked by adenosine. Furthermore, BV2-st medium induced a similar AMPA-current depression in CX3CR1GFP/GFP hippocampal neurons and this depression was again blocked by DPCPX. We also report that CX3CL1 induced a significant release of adenosine from microglial BV2 cells, as measured by HPLC analysis. We demonstrate that (i) CX3CL1, along with AR1, are critical players for counteracting Glu-mediated neurotoxicity in the brain and (ii) AR1 mediates neuromodulatory action of CX3CL1 on hippocampal neurons.

show abstract

“…There are reports that adenosine suppresses the proliferation of murine BM-derived macrophages (43), but this effect is mediated by the A2b receptor. A2a stimulation promotes internalization of chemokine receptors (44), thereby limiting emigration of leukocytes from the blood into the tissue. This effect could also impact on monocyte and neutrophil efflux from the BM, a process controlled by chemokine receptors.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Anti-Inflammatory Effects of Myeloid Cell Adenosine Receptor A2a Stimulation in Lipopolysaccharide-Induced Lung Injury

Reutershan

Cagnina

Chang

et al. 2007

The Journal of Immunology

117

120

View full text Add to dashboard Cite

To determine the role of the adenosine receptor A2a in a murine model of LPS-induced lung injury, migration of polymorphonuclear leukocytes (PMNs) into the different compartments of the lung was determined by flow cytometry, microvascular permeability was assessed by the extravasation of Evans blue, and the release of chemotactic cytokines into the alveolar airspace was determined by ELISA. Measurements were performed in wild-type and A2a gene-deficient mice (A2a−/−). To differentiate the role of A2a on hemopoietic and nonhemopoietic cells, we created chimeric mice by transfer of bone marrow (BM) between wild-type and A2a−/− mice and used mice that lacked A2a expression selectively on myeloid cells (A2aflox/flox × LysM-cre). A specific A2a receptor agonist (ATL202) was used to evaluate its potential to reduce lung injury in vivo. In wild-type mice, therapeutic treatment with ATL202 reduced LPS-induced PMN recruitment, and release of cytokines. Pretreatment, but not posttreatment, also reduced Evans blue extravasation. In the BM chimeric mice lacking A2a on BM-derived cells, PMN migration into the alveolar space was increased by ∼50%. These findings were confirmed in A2aflox/flox × LysM-cre mice. ATL202 was only effective when A2a was present on BM-derived cells. A2a agonists may be effective at curbing inflammatory lung tissue damage.

show abstract

Adenosine A2a receptors induce heterologous desensitization of chemokine receptors

Cited by 57 publications

References 33 publications

Activation of the A₃Adenosine Receptor Suppresses Superoxide Production and Chemotaxis of Mouse Bone Marrow Neutrophils

Activation of the A₃Adenosine Receptor Suppresses Superoxide Production and Chemotaxis of Mouse Bone Marrow Neutrophils

Activity of Adenosine Receptors Type 1 Is Required for CX3CL1-Mediated Neuroprotection and Neuromodulation in Hippocampal Neurons

Therapeutic Anti-Inflammatory Effects of Myeloid Cell Adenosine Receptor A2a Stimulation in Lipopolysaccharide-Induced Lung Injury

Contact Info

Product

Resources

About

Adenosine A2a receptors induce heterologous desensitization of chemokine receptors

Cited by 57 publications

References 33 publications

Activation of the A3Adenosine Receptor Suppresses Superoxide Production and Chemotaxis of Mouse Bone Marrow Neutrophils

Activation of the A3Adenosine Receptor Suppresses Superoxide Production and Chemotaxis of Mouse Bone Marrow Neutrophils

Activity of Adenosine Receptors Type 1 Is Required for CX3CL1-Mediated Neuroprotection and Neuromodulation in Hippocampal Neurons

Therapeutic Anti-Inflammatory Effects of Myeloid Cell Adenosine Receptor A2a Stimulation in Lipopolysaccharide-Induced Lung Injury

Contact Info

Product

Resources

About

Activation of the A₃Adenosine Receptor Suppresses Superoxide Production and Chemotaxis of Mouse Bone Marrow Neutrophils

Activation of the A₃Adenosine Receptor Suppresses Superoxide Production and Chemotaxis of Mouse Bone Marrow Neutrophils