P182 Adenosine potentiates human mast cell fibrinolytic activity

We investigated whether adenosine, a potent contributor to the regulation of pulmonary function, can modulate human lung mast cell (HLMC) fibrinolytic activity. Tissue plasminogen activator (tPA) activity and tPA transcript expression levels from a human mast cell line (HMC-1) and HLMC were monitored following adenosine application. Adenosine potentiated mast cell tPA activity and tPA gene expression in a dose-dependent manner. Adenosine effects were abolished in the presence of adenosine deaminase. HMC-1 cells predominantly expressed adenosine A 2A and A 2B receptor transcripts (A 2A >>A 2B >A 3 >>A 1 ). In addition to A 2A and A 2B , A 3 receptor transcripts were also abundantly found in HLMC (A 2A >>A 2B >>A 3 >>A 1 ). Pharmacological and signalling studies suggest that the A 2A receptor is the major subtype accounting for adenosine-induced mast cell tPA activity. Finally, the supernatant from HMC-1 cells treated with adenosine (24h) significantly increased fibrin clot lysis, while ZM241385, an A 2A receptor antagonist, abolished this effect. This study provides the first data to demonstrate the potentiating effect of adenosine on mast cell tPA activity and fibrin clot lysis.