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Infection and Immunity, March 2004, p. 1349-1357, Vol. 72, No. 3
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.3.1349-1357.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Regulation of Adenosine Receptor Subtypes during Cultivation of Human Monocytes: Role of Receptors in Preventing Lipopolysaccharide-Triggered Respiratory Burst

Andrea Thiele,^1, Romy Kronstein,^1, Anne Wetzel,^1, Anja Gerth,¹ Karen Nieber,² and Sunna Hauschildt^1*

Institute of Zoology, Department of Immunobiology,¹ Institute of Pharmacy, Department of Pharmacology for Natural Sciences, University of Leipzig, D-04103 Leipzig, Germany²

Received 13 June 2003/ Returned for modification 29 July 2003/ Accepted 10 December 2003

Adenosine is a potent anti-inflammatory agent that modulates the function of cells involved in the inflammatory response. Here we show that it inhibits lipopolysaccharide (LPS)-induced formation of reactive oxygen intermediates (ROI) in both freshly isolated and cultured human monocytes. Blocking of adenosine uptake and inactivation of the adenosine-degrading enzyme adenosine deaminase enhanced the inhibitory action of adenosine, indicating that both pathways regulate the extracellular adenosine concentration. Adenosine-mediated inhibition could be reversed by XAC (xanthine amine congener), an antagonist of the adenosine receptor A_2A, and MRS 1220 {N-9-chloro-2-(2-furanyl)[1, 2, 4]-triazolo[1,5-c]quinazolin-5-benzeneacetamide}, an A₃ receptor antagonist, in both cell populations, while DPCPX (1,3-dipropyl-8-cyclopentylxanthine), an A₁ receptor antagonist, had no effect. Similar to what was seen with adenosine, CGS 21680, an A_2A and A₃ receptor agonist, and IB-MECA, a nonselective A₁ and A₃ receptor agonist, dose dependently prevented ROI formation, indicating the involvement of A₃ and probably also A_2A in the suppressive effect of adenosine. Pretreatment of monocytes with adenosine did not lead to changes in the LPS-induced increase in intracellular calcium levels ([Ca²⁺]_i). Thus, participation of [Ca²⁺]_i in the action of adenosine seems unlikely. The adenosine-mediated suppression of ROI production was found to be more pronounced when monocytes were cultured for 18 h, a time point at which changes in the mRNA expression of adenosine receptors were observed. Most prominent was the increase in the A_2A receptor mRNA. These data demonstrate that cultivation of monocytes is accompanied by changes in the inhibitory action of adenosine mediated by A₃ and probably also the A_2A receptor and that regulation of adenosine receptors is an integral part of the monocyte differentiation program.

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* Corresponding author. Mailing address: Institute of Zoology, Department of Immunobiology, University of Leipzig, Bruederstrasse 32, D-04103 Leipzig, Germany. Phone: 49 341-9736747. Fax: 49 341-9736848. E-mail: shaus{at}rz.uni-leipzig.de.

Editor: S. H. E. Kaufmann

Present address: Hubrecht Laboratorium for Developmental Biology, NL-3584 CT Utrecht, The Netherlands.

Present address: Institute of Physiology, Medical Faculty, Technical University Dresden, D-01307 Dresden, Germany.

Present address: Department of Dermatology, University Hospital Leipzig, D-04103 Leipzig, Germany.

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Infection and Immunity, March 2004, p. 1349-1357, Vol. 72, No. 3
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.3.1349-1357.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

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