A. Schmidt-choudhury et al., Stem cell factor influences neuro-immune interactions: The response of mast cells to pituitary adenylate cyclase activating polypeptide is altered bystem cell factor, REGUL PEPT, 83(2-3), 1999, pp. 73-80
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.