Just parking.
J Clin Invest, February 2000, Volume 105, Number 3, 361-367
Copyright ¸2000 by the American Society for Clinical Investigation
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Article
Adenosine and inosine increase cutaneous vasopermeability by activating A3 receptors on mast cells
Stephen L. Tilley1, Victoria A. Wagoner1, Christopher A. Salvatore2, Marlene A. Jacobson2 and Beverly H. Koller1
1 Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of North Carolina?Chapel Hill, Chapel Hill, North Carolina 27599, USA 2 Department of Pharmacology, Merck Research Labs, West Point, Pennsylvania 19486, USA
Address correspondence to: Beverly H. Koller, 7027 Thurston-Bowles Building, University of North Carolina?Chapel Hill, Chapel Hill, North Carolina 27599-7248, USA. Phone: (919) 962-2153; Fax: (919) 966-7524; E-mail: treawouns@aol.com.
Received for publication August 25, 1999, and accepted in revised form December 10, 1999.
Adenosine has potent effects on both the cardiovascular and immune systems. Exposure of tissues to adenosine results in increased vascular permeability and extravasation of serum proteins. The mechanism by which adenosine brings about these physiological changes is poorly defined. Using mice deficient in the A3 adenosine receptor (A3AR), we show that increases in cutaneous vascular permeability observed after treatment with adenosine or its principal metabolite inosine are mediated through the A3AR. Adenosine fails to increase vascular permeability in mast cell?deficient mice, suggesting that this tissue response to adenosine is mast cell?dependent. Furthermore, this response is independent of activation of the high-affinity IgE receptor (FcR1) by antigen, as adenosine is equally effective in mediating these changes in FcR1 á-chain?deficient mice. Together these results support a model in which adenosine and inosine induce changes in vascular permeability indirectly by activating mast cells, which in turn release vasoactive substances. The demonstration in vivo that adenosine, acting through a specific receptor, can provoke degranulation of this important tissue-based effector cell, independent of antigen activation of the high-affinity IgE receptor, supports an important role for this nucleoside in modifying the inflammatory response. |
