EFFECTS OF NERVE GROWTH-FACTOR (NGF) AND OTHER FIBROBLAST-DERIVED GROWTH-FACTORS ON IMMATURE HUMAN MAST-CELLS (HMC-1)

We have previously shown that fibroblast and keratinocyte supernatants up-regulate expression of mast cell characteristics in the human imma ture mast cell line HMC-1. This effect could not be induced in HMC-1 c ells by the well-known mast cell growth factor stem cell factor (SCF), probably due to mutations of the SCF receptor c-Kit in these cells. H ere we report the effects of several known fibroblast- and keratinocyt e-derived growth factors, namely nerve growth factor (NGF), basic fibr oblast growth factor, platelet-derived growth factor and transforming growth factor-beta, on mast cell differentiation, using HMC-1 cells as a model. NGF, at 0.1-50 ng/ml concentrations, caused a marked, dose-d ependent up-regulation of tryptase, Fc epsilon RI and histamine within 10 days of culture, associated with an enhanced expression of mRNA fo r Fc epsilon RI and mast cell tryptase. On restriction analysis, only mast cell beta-tryptase, but not alpha-tryptase, could be demonstrated . Furthermore, the high-affinity NGF receptor (TrkA) was found at both the transcriptional and protein levels, while expression of the low-a ffinity NGF receptor was detectable at the mRNA level only. None of th e other growth factors caused a significant alteration of the mast cel l markers studied when added to HMC-1 cells at concentrations known to be biologically active in other culture systems. Immature human mast cells are thus induced to assume a more mature phenotype in vitro in r esponse to NGF, most probably via stimulation of the high-affinity NGF receptor expressed on these cells. Besides SCF, NGF should therefore be considered as an additional mast cell growth factor that contribute s to human mast cell maturation at tissue sites.