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Published online before print December 30, 2005

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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0505249

Received for publication May 9, 2005.
Revised November 2, 2005.
Accepted for publication November 15, 2005.

Article

Differential expression of adenosine receptors in human neutrophils: up-regulation by specific Th1 cytokines and lipopolysaccharide

Centre de Recherche en Rhumatologie et Immunologie, Centre Hospitalier Universitaire de Québec, Pavillon C.H.U.L. et Université Laval, Département d’Anatomie et de Physiologie, Canada

^@ To whom correspondence should be addressed. E-mail: Sylvain.Bourgoin{at}crchul.ulaval.ca.

	Abstract

Four types of adenosine receptors have been identified in different tissues and cell types, namely, A₁, A_2A, A_2B, and A₃ receptors. We report that A_2AR but not A_2BR mRNA in freshly isolated polymorphonuclear neutrophils (PMN) is maximally up-regulated after 4 h stimulation with lipopolysaccharide (LPS) or tumor necrosis factor (TNF-) and to a lesser extent, with interleukin (IL)-1. These effects were maintained up to 21 h. Consistent with changes in A_2AR mRNA expression, up-regulation of A_2AR protein was also detected after 4 h of LPS or TNF- exposure. Up-regulation of A_2AR protein expression was transient and returned to near basal levels after 12 h or 16 h stimulation with TNF- or LPS, respectively. Conversely, IL-1 failed to promote A_2AR protein expression. Suppression of thapsigargin-induced leukotriene synthesis by the selective A_2AR agonist CGS-21680 was found to be more pronounced when PMN were cultured for 4 h with LPS or TNF-. In contrast, the up-regulation of A_2AR 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_2AR 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_2AR up-regulation varied depending on the stimulus used to stimulate PMN functional responses after their incubation with proinflammatory mediators.

Key Words: A_2AR • TNF- • leukotrienes

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