title: Adenosine potentiates human lung mast cell tissue plasminogen activator activity.
abstract: 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 and HLMC predominantly expressed adenosine A(2A) and A(2B) receptor transcripts (A(2B) ≈ A(2A) > A(3) >> A(1)). Pharmacological and signaling 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 and HLMC treated with adenosine (for 24 h) significantly increased fibrin clot lysis, whereas ZM241385, an A(2A) receptor antagonist, abolished this effect. To our knowledge, this study provides the first data to demonstrate the potentiating effect of adenosine on mast cell tPA activity and fibrin clot lysis.
authors.affiliation: Department of Cell Physiology and Pharmacology, University of Leicester, Leicester LE1 9HN, United Kingdom.
authors.forename: Michal J
authors.initials: MJ
authors.lastname: Sereda
authors.forename: Peter
authors.initials: P
authors.lastname: Bradding
authors.forename: Catherine
authors.initials: C
authors.lastname: Vial
mesh_terms: D000241:Adenosine / Q000494:pharmacology*; D001780:Blood Coagulation Tests; D002460:Cell Line; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D005342:Fibrinolysis / Q000502:physiology; D006801:Humans; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D043705:Receptor, Adenosine A2A / Q000378:metabolism; D010959:Tissue Plasminogen Activator / Q000096:biosynthesis / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
chemical_list: D043705:Receptor, Adenosine A2A; D010959:Tissue Plasminogen Activator; D000241:Adenosine