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Differential expression of adenosine receptors in human neutrophils: up‐regulation by specific Th1 cytokines and lipopolysaccharide
Author(s) -
Fortin Andrée,
Harbour Danielle,
Fernandes Maria,
Borgeat Pierre,
Bourgoin Sylvain
Publication year - 2006
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0505249
Subject(s) - biology , lipopolysaccharide , adenosine , receptor , microbiology and biotechnology , adenosine receptor , immunology , differential (mechanical device) , purinergic signalling , adenosine a3 receptor , endocrinology , biochemistry , agonist , aerospace engineering , engineering
Four types of adenosine receptors have been identified in different tissues and cell types, namely, A 1 , A 2A , A 2B , and A 3 receptors. We report that A 2A R but not A 2B R mRNA in freshly isolated polymorphonuclear neutrophils (PMN) is maximally up‐regulated after 4 h stimulation with lipopolysaccharide (LPS) or tumor necrosis factor α (TNF‐α) and to a lesser extent, with interleukin (IL)‐1β. These effects were maintained up to 21 h. Consistent with changes in A 2A R mRNA expression, up‐regulation of A 2A R protein was also detected after 4 h of LPS or TNF‐α exposure. Up‐regulation of A 2A R protein expression was transient and returned to near basal levels after 12 h or 16 h stimulation with TNF‐α or LPS, respectively. Conversely, IL‐1β failed to promote A 2A R protein expression. Suppression of thapsigargin‐induced leukotriene synthesis by the selective A 2A R agonist CGS‐21680 was found to be more pronounced when PMN were cultured for 4 h with LPS or TNF‐α. In contrast, the up‐regulation of A 2A R has no impact on CGS‐21680‐induced inhibition of phospholipase D activation and superoxide production in response to formyl‐Met‐Leu‐Phe. These results demonstrate that the A 2A R is up‐regulated by specific T helper cell type 1 cytokines and LPS. Although this could represent a potential feedback mechanism to control inflammation, the effect of A 2A R up‐regulation varied depending on the stimulus used to stimulate PMN functional responses after their incubation with proinflammatory mediators.