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

A. Schmidt-Choudhury*, J. Meissner, J. Seebeck, E. J. Goetzl, M. Xia, S. J. Galli, W. E. Schmidt, J. Schaub, B. K. Wershil

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Mast cells degranulation can be elicited by a number of biologically important neuropeptides, but the mechanisms involved in mast cell-neuropeptide interactions have not been fully elucidated. Stem cell factor (SCF), also known as c-kit or kit ligand, induces multiple effects on mast cells, including proliferation, differentiation, maturation, and prevents apoptosis. We investigated the ability of SCF to affect mast cell responsiveness to the neuropeptides pituitary adenylate cyclase activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP). PACAP 1-27, PACAP1-38, or VIP failed to induced preformed mediator release from mouse bone-marrow-cultured mast cells (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 3H-hydroxytrypamine (5-HT) release in response to PACAP peptides or VIP. Deoxyglucose and the mitochondrial inhibitor antimycin significantly inhibited PACAP-induced 5-HT release indicating that the central event induced by PACAP peptides was exocytosis. The G(α)i inhibitor, pertussis toxin, significantly diminished PACAP-induced 5-HT release from BMCMCs in SCF suggesting the involvement of heterotrimeric G-proteins. Western blot analysis using antibodies directed against the human VIP type I/PACAP type II receptor demonstrated a 70-72 kD immunoreactive protein expressed in greater amounts in BMCMC grown in SCF compared with BMCMC in CM. We conclude that SCF induces a mast cell population that is responsive to PACAPs and VIP involving a heterotrimeric G-protein-dependent mechanism. Copyright (C) 1999 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)73-80
Number of pages8
JournalRegulatory Peptides
Volume83
Issue number2-3
DOIs
StatePublished - 1999

Funding

We thank Ingrid Berg and Jackie A. Lavigne for expert technical assistance. Rat recombinant stem cell factor was kindly provided by Dr. K. Langley (AMGEN, Thousand Oaks, CA). This work was supported by NIH grants DK33506 and DK46819 (B.K.W.), AI 29912 (E.J.G.) and CA72074 and AI23990 (S.J.G.) and grants from the Deutsche Forschungsgemeinschaft Schm 805/4-2 (W.E.S.) Ro 819-1/1 and Schm 1223/4-1(A.S.-C.)

Keywords

  • Mast cells
  • Neuropeptides
  • Pituitary adenylate cyclase activating polypeptide
  • Vasoactive intestinal polypeptide

ASJC Scopus subject areas

  • Endocrinology
  • Cellular and Molecular Neuroscience
  • Biochemistry
  • Physiology
  • Clinical Biochemistry

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