REGULATION OF HUMAN MAST-CELL AND BASOPHIL FUNCTION BY CAMP

1. Mast cells and basophils are important in mediating allergic disord ers such as asthma. Activation of these cells results in the release o f a wide variety of mediators that can promote inflammatory responses. 2. Receptor-mediated activators of adenylate cyclase such as the P-ad renoceptor agonist, isoprenaline, and prostaglandin E-2 (PGE(2)) are e ffective at inhibiting mediator release from human lung mast cells (HL MC) but not basophils. In HLMC, both isoprenaline and PGE(2) elevate a nd sustain increases in cyclic adenosine 3',5'-monophosphate (cAMP) wh ereas in basophils, both compounds cause transient increases in cAMP. 3. Non selective inhibitors of phosphodiesterase (PDE) such as theophy lline and 3-isobutyl-1-methylxanthine are effective inhibitors of medi ator release from both HLMC and basophils and both compounds cause ele vations of cAMP that are sustained in both cell types. 4. Studies with selective inhibitors of PDE indicate that the cAMP specific PDE, PDE 4, regulates the activity of basophils but not HLMC. The nature of the PDE regulating HLMC responses is uncertain. 5. These data indicate th at agents that induce and sustain elevations in intracellular cAMP att enuate the stimulated release of mediators from mast cells and basophi ls. However, the responsiveness of HLMC and basophils to selected cAMP -active agents differs. (C) 1998 Elsevier Science Inc.