Adenosine, mast cells and asthma.
The aim of this article is to review the interplay between adenosine and mast cells in asthma. Adenosine is an endogenous nucleoside released from metabolically active cells and generated extracellularly via the degradation of released ATP. It is a potent biological mediator that modulates the activity of numerous cell types including platelets, neutrophils and mast cells via action at specific adenosine receptors (A1, A2a, A2b, A3). These receptors are expressed on mast cells but the exact pattern of receptor subtype expression depends on the source of the mast cells. Adenosine is also a potent bronchoconstricting agent and is suggested to contribute to the pathophysiology of asthma. Evidence is provided to suggest that the nucleoside exerts its influence on the asthmatic condition through its ability to modulate the release of mast cell derived mediators. However, the mechanism of adenosine/mast cell interaction which contributes to asthma remains unclear. Progress in the area has been hampered by the heterogeneity of mast cell responses and a lack of highly specific receptor agonists and antagonists. The expression of different adenosine receptor subtypes on mast cells is described. The final section of the review presents data to suggest that BAL mast cells may provide an accurate and relevant model for future investigations and together with the development of superior pharmacological tools, may aid the realisation of the therapeutic potential of adenosine/mast cell interactions in asthma. In conclusion, the role of adenosine in asthma is clearly complex. A better understanding of the contribution of adenosine to the asthmatic condition may lead to novel therapeutic approaches in the treatment of the disease.
Forsythe
P
P
Department of Clinical Biochemistry, The Queen's University of Belfast, UK.
Ennis
M
M
D000241:Adenosine / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D001249:Asthma / Q000503:physiopathology*; D001980:Bronchi / Q000187:drug effects; D018893:Bronchoalveolar Lavage; D006801:Humans; D066298:In Vitro Techniques; D008407:Mast Cells / Q000378:metabolism / Q000502:physiology*; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists
D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D000241:Adenosine