Release of Adenosine from Human Sensitized Lung Fragments and its Effect on Antigen-induced Mediator Release

Abstract

Adenosine may play a role in asthma as a pro-inflammatory mediator. In this study, the release of adenosine from human sensitized lung fragments and its effect on antigen-induced histamine and leukotriene release has been explored. Antigen challenge increased histamine and leukotriene release five-fold but was without effect on adenosine release. In contrast, the adenosine deaminase inhibitor EHNA (10 μ M) and the adenosine kinase inhibitor 5-iodotubericidin (10 μ M) increased adenosine concentration 45-fold ( P ≤ 0.001; n= 4 patients). Of major interest was the finding that the non-selective, cell impermeant, adenosine antagonist pSPT (100 μ M) decreased histamine and leukotriene release by 25% ( P ≤ 0.001) and 40%, respectively ( P ≤ 0.05; n= 9 patients). Additionally, the non-selective adenosine agonist NECA (10 μ M) markedly inhibited antigen-induced leukotriene release by 80– 90% ( P ≤ 0.001) and marginally inhibited histamine release by approximately 10% ( P ≤ 0.05; n=9); the A 2a-selective agonist DPMA (10 μ M) was without effect on either histamine or leukotriene release. These results are consistent with adenosine having a biphasic effect on antigen-induced mediator release with low concentrations potentiating release and high concentrations inhibiting release. The overall stimulatory effect of endogenous adenosine supports the proposal that adenosine may act as a pro-inflammatory mediator in asthma.