Adenosine and inosine increase cutaneous vasopermeability by activating A3 receptors on mast cells
Stephen L. Tilley, … , Marlene A. Jacobson, Beverly H. Koller
Stephen L. Tilley, … , Marlene A. Jacobson, Beverly H. Koller
Published February 1, 2000
Citation Information: J Clin Invest. 2000;105(3):361-367. https://doi.org/10.1172/JCI8253.
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Adenosine and inosine increase cutaneous vasopermeability by activating A3 receptors on mast cells

Abstract

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 (FcεR1) by antigen, as adenosine is equally effective in mediating these changes in FcεR1 β-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.

Authors

Stephen L. Tilley, Victoria A. Wagoner, Christopher A. Salvatore, Marlene A. Jacobson, Beverly H. Koller

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Plasma protein extravasation after intradermal adenosine and inosine in ...
Plasma protein extravasation after intradermal adenosine and inosine in wild-type (+/+), A3AR-deficient (A3AR–/–), mast cell–deficient (W/WV), and FcεR1 β-chain–deficient mice (FcεR1–/–). Mice were injected intravenously with 100 μL of 1% Evans blue in PBS. One hour later, 20 μL of adenosine 10–3 M or inosine 10–4 M (a), or adenosine 10–4 M (b), was injected intradermally into the right ear of each animal. Control ears (left ears) were injected with 20 μL of PBS. One hour after intradermal injections, 7-mm ear biopsies were obtained and placed in formamide at 57°C for 48 hours to extract dye. Plasma protein extravasation was quantitated by measuring OD at 610 nm. Data represent the mean difference in OD between PBS-treated ears and nucleoside-treated ears, ± SEM. n = number of animals in each group. *P < 0.005.