| Résumé | Anaphylatoxin C3a and adenosine receptors (AR) are implicated in the inflammatory process associated with allergic rhinitis and asthma by modifying mast cell (MC) responses. Possible interactions between these G-protein coupled receptor (GPCR) pathways in MCs have not yet been demonstrated. LAD2 human MC were stimulated with C3a in the presence or absence of AR agonists and antagonists and their adhesion, chemotaxis and mediator release were measured. The pan-specific AR agonist, 5′-N-Ethylcarboxamidoadenosine (NECA) inhibited C3a-induced LAD2 cell migration, adhesion, degranulation, production of CCL2, and ERK1/2 phosphorylation. The selective A2A receptor agonist CGS 21680 inhibited C3a-mediated degranulation, while the A2B and A3 receptor agonists BAY 60-6583 and IB-MECA, respectively, had no effect. Moreover, an A2A receptor antagonist SCH 58261 blocked the inhibitory effect of NECA on C3a-induced degranulation, suggesting that inhibition of degranulation was mediated through the A2A receptor. NECA increased intracellular cAMP in C3a-activated mast cells, suggesting that Gαs protein signals are required for adenosine-induced inhibition of C3a-mediated human mast cell activation. The adenylyl cyclase inhibitor SQ 22536 attenuated the inhibitory effect of NECA on C3a-activated degranulation, and the A2A agonist CSG 21680 potentiated the inhibition of mast cell activation mediated by the A2A receptor. Our results suggest that adenosine inhibits C3a-mediated activation of human mast cells, possibly through a Gαs protein-dependent pathway. |
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