Stem cell factor influences neuro-immune interactions: The response of mast cells to pituitary adenylate cyclase activating polypeptide is altered bystem cell factor

Mast cells degranulation can be elicited by a number of biologically import ant neuropeptides, but the mechanisms involved in mast cell-neuropeptide in teractions have not been fully elucidated. Stem cell factor (SCF), also kno wn as c-kit or kit ligand, induces multiple effects on mast cells, includin g proliferation, differentiation, maturation, and prevents apoptosis. We in vestigated the ability of SCF to affect mast cell responsiveness to the neu ropeptides pituitary adenylate cyclase activating polypeptide (PACAP) and v asoactive intestinal peptide (VIP). PACAP 1-27, PACAP1-38, or VIP failed to induced preformed mediator release from mouse bone-marrow-cultured mast ce lls (BMCMC) derived in concanavalin A-stimulated spleen conditioned medium (CM). By contrast, BMCMC grown in SCF-containing medium or freshly isolated peritoneal mast cells exhibited significant H-3-hydroxytrypamine (5-MT) re lease in response to PACAP peptides or VIP. Deoxyglucose and the mitochondr ial inhibitor antimycin significantly inhibited PACAP-induced 5-HT release indicating that the central event induced by PACAP peptides was exocytosis. The G(alpha)i inhibitor, pertussis toxin, significantly diminished PACAP-i nduced 5-HT release from BMCMCs in SCF suggesting the involvement of hetero trimeric G-proteins. Western blot analysis using antibodies directed agains t the human VIP type I/PACAP type II receptor demonstrated a 70-72 kD immun oreactive protein expressed in greater amounts in BMCMC grown in SCF compar ed with BMCMC in CM. We conclude that SCF induces a mast cell population th at is responsive to PACAPs and VIP involving a heterotrimeric G-protein-dep endent mechanism. (C) 1999 Elsevier Science B.V. All rights reserved.