Release of adenosine from human sensitized lung fragments and its effect on antigen-induced mediator release

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 mu M) and the adenosine kinase inhibitor 5-iodotubericidin (10 mu M) increased adenosine concentration 45-fold (P less than or equal to 0.001; n=4 patients). Of major interest was the finding that the non-selective, cell impermeant, adenosine antagonist pSPT (100 mu M) decreased histamine and leukotriene release by 25% (P less than or equal to 0.001) and 40%, respectively (P less than or equal to 0.05; n=9 patients). Additionally, the non-selective adenosine agonist NECA (10 mu M) markedly inhibited antigen-induced leukotriene release by 80-90% (P less than or equal to 0.001) and marginally inhibited histamine release by approximately 10% (P less than or equal to 0.05; n=9); the A(2a)-selective agonist DPMA (10 mu 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. (C) 1996 Academic Press Limited.