Journal article
Activation of the A3 adenosine receptor suppresses superoxide production and chemotaxis of mouse bone marrow neutrophils
Molecular pharmacology, Vol.74(3), pp.685-696
09/2008
DOI: 10.1124/mol.108.048066
PMID: 18583455
Abstract
Adenosine is formed in injured/ischemic tissues, where it suppresses the actions of essentially all cells of the immune system. Most of the anti-inflammatory actions of adenosine have been attributed to signaling through the Gs protein-coupled A2A adenosine receptor (AR). Here, we report that the A3AR is highly expressed in murine neutrophils isolated from bone marrow. Selective activation of the A3AR with (2S,3S,4R,5R)-3-amino-5-[6-(2,5-dichlorobenzylamino)purin-9-yl]-4-hydroxytetrahydrofuran-2-carboxylic acid methylamide (CP-532,903) potently inhibited mouse bone marrow neutrophil superoxide generation and chemotaxis induced by various activating agents. The selectivity of CP-532,903 was confirmed in assays using neutrophils obtained from A2AAR and A3AR gene “knockout” mice. In a model of thioglycollate-induced inflammation, treating mice with CP-532,903 inhibited recruitment of leukocytes into the peritoneum by specifically activating the A3AR. Collectively, our findings support the theory that the A3AR contributes to the anti-inflammatory actions of adenosine on neutrophils and provide a potential mechanistic explanation for the efficacy of A3AR agonists in animal models of inflammation (i.e., inhibition of neutrophil-mediated tissue injury).
Details
- Title: Subtitle
- Activation of the A3 adenosine receptor suppresses superoxide production and chemotaxis of mouse bone marrow neutrophils
- Creators
- Dharini Van Der Hoeven - Medical College of WisconsinTina C. Wan - Medical College of WisconsinJohn A. Auchampach - Medical College of Wisconsin
- Resource Type
- Journal article
- Publication Details
- Molecular pharmacology, Vol.74(3), pp.685-696
- DOI
- 10.1124/mol.108.048066
- PMID
- 18583455
- ISSN
- 0026-895X
- eISSN
- 1521-0111
- Publisher
- AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
- Number of pages
- 12
- Grant note
- R01HL077707 / National Heart, Lung, and Blood Institute (http://data.elsevier.com/vocabulary/SciValFunders/100000050) National Heart, Lung, and Blood Institute (http://data.elsevier.com/vocabulary/SciValFunders/100000050)
- Language
- English
- Date published
- 09/2008
- Academic Unit
- Oral Pathology, Radiology and Medicine; Dentistry Administration
- Record Identifier
- 9985157546002771
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