Faculty Collaboration Database

Activation of the A(3) adenosine receptor suppresses superoxide production and chemotaxis of mouse bone marrow neutrophils. Mol Pharmacol 2008 Sep;74(3):685-96

Date

06/28/2008

Pubmed ID

18583455

Pubmed Central ID

PMC2574951

DOI

10.1124/mol.108.048066

Scopus ID

2-s2.0-50449094182 (requires institutional sign-in at Scopus site)   71 Citations

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 G(s) protein-coupled A(2A) adenosine receptor (AR). Here, we report that the A(3)AR is highly expressed in murine neutrophils isolated from bone marrow. Selective activation of the A(3)AR 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 A(2A)AR and A(3)AR 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 A(3)AR. Collectively, our findings support the theory that the A(3)AR contributes to the anti-inflammatory actions of adenosine on neutrophils and provide a potential mechanistic explanation for the efficacy of A(3)AR agonists in animal models of inflammation (i.e., inhibition of neutrophil-mediated tissue injury).

Author List

van der Hoeven D, Wan TC, Auchampach JA

Authors

John A. Auchampach PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
Tina C. Wan PhD Research Scientist II in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adenosine
Animals
Bone Marrow Cells
Cell Separation
Chemotaxis
Furans
Gene Expression Regulation
Humans
Inflammation
Mice
Mice, Inbred C57BL
Mice, Knockout
N-Formylmethionine Leucyl-Phenylalanine
Neutrophil Activation
Neutrophils
Peritonitis
Phenethylamines
Purines
RNA, Messenger
Receptor, Adenosine A2A
Receptor, Adenosine A2B
Receptor, Adenosine A3
Superoxides