PMID- 8698398 OWN - NLM STAT- MEDLINE DCOM- 19960905 LR - 20190512 IS - 0019-2805 (Print) IS - 1365-2567 (Electronic) IS - 0019-2805 (Linking) VI - 87 IP - 2 DP - 1996 Feb TI - Stem cell factor enhances immunoglobulin E-dependent mediator release from cultured rat bone marrow-derived mast cells: activation of previously unresponsive cells demonstrated by a novel ELISPOT assay. PG - 326-33 AB - Mucosal mast cells (MMC) are important effector cells in the immune response against gastrointestinal nematodes. We used cultured rat bone marrow-derived mast cells (BMMC) as an in vitro model of MMC to study the effects of the multifunctional cytokine stem cell factor (SCF) on immunoglobulin E (IgE)-dependent secretion of granule mediators. SCF (< or = 1000 ng/ml) was not a direct secretagogue for these cells, but it significantly enhanced IgE-mediated secretion of the granule constituents rat mast cell protease-II (RMCP-II) and beta-hexosaminidase from mature BMMC in a dose-dependent manner (> 10 ng/ml). Maximum up-regulation of secretion occurred after cells were pretreated with SCF (50 ng/ml) for 5 minutes before challenge with anti-IgE, but the effect then declined and was absent in cells incubated with the cytokine for 3 to 24 h. In a novel ELISPOT assay developed to identify individual BMMC secreting RMCP-II, the proportion of mature BMMC responding to anti-IgE was significantly increased by treatment with SCF. To investigate this effect further, the percentage release of RMCP-II and beta-hexosaminidase from populations of mature BMMC was directly compared to the proportion of individual cells releasing RMCP-II as detected by ELISPOT. The release of both mediators was enhanced by SCF, and the increased percentage release reflected both an increased proportion of secreting cells, and enhanced mediator release from individual cells. These results suggest that SCF can enhance IgE-dependent mediator release from BMMC not only by augmenting the secretory response from individual cells, but also by activating previously unresponsive cells. FAU - Hill, P B AU - Hill PB AD - Department of Preclinical Veterinary Sciences, University of Edinburgh, UK. FAU - MacDonald, A J AU - MacDonald AJ FAU - Thornton, E M AU - Thornton EM FAU - Newlands, G F AU - Newlands GF FAU - Galli, S J AU - Galli SJ FAU - Miller, H R AU - Miller HR LA - eng GR - AI 22674/AI/NIAID NIH HHS/United States GR - AI 23990/AI/NIAID NIH HHS/United States GR - Wellcome Trust/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - England TA - Immunology JT - Immunology JID - 0374672 RN - 0 (Stem Cell Factor) RN - 37341-29-0 (Immunoglobulin E) RN - EC 3.2.1.52 (beta-N-Acetylhexosaminidases) RN - EC 3.4.21.- (Serine Endopeptidases) RN - EC 3.4.21.- (chymase 2) RN - EC 3.4.21.- (cytotoxic T lymphocyte-specific serine protease) RN - EC 3.4.21.39 (Chymases) SB - IM MH - Animals MH - Bone Marrow/immunology/*metabolism MH - Cell Culture Techniques MH - Chymases MH - Dose-Response Relationship, Immunologic MH - Immunoenzyme Techniques MH - Immunoglobulin E/*physiology MH - Kinetics MH - Male MH - Mast Cells/immunology/*metabolism MH - Rats MH - Rats, Wistar MH - Serine Endopeptidases/*metabolism MH - Stem Cell Factor/*pharmacology MH - beta-N-Acetylhexosaminidases/*metabolism PMC - PMC1384292 EDAT- 1996/02/01 00:00 MHDA- 1996/02/01 00:01 PMCR- 1997/02/01 CRDT- 1996/02/01 00:00 PHST- 1996/02/01 00:00 [pubmed] PHST- 1996/02/01 00:01 [medline] PHST- 1996/02/01 00:00 [entrez] PHST- 1997/02/01 00:00 [pmc-release] AID - 10.1046/j.1365-2567.1996.455545.x [doi] PST - ppublish SO - Immunology. 1996 Feb;87(2):326-33. doi: 10.1046/j.1365-2567.1996.455545.x.