EXPRESSION OF FUNCTIONAL TRKA RECEPTOR TYROSINE KINASE IN THE HMC-1 HUMAN MAST-CELL LINE AND IN HUMAN MAST-CELLS

Nerve growth factor (NGF) can influence mast cell development and func tion in murine rodents by interacting with its receptors on mast cells . We now report the identification of mRNA transcripts of full-length tyrosine kinase-containing trkA, trkB, and trkC neurotrophin receptor genes in HMC-1 human mast cell leukemia cells, Although HMC-1 cells la cked p75 mRNA, they expressed transcripts for the exon-lacking splice variant of trkA (trkAl), truncated trkB (trkB.T1), and truncated trkC, By flow cytometry, HMC-1 cells exhibited expression of TrkA, TrkB, an d TrkC receptor proteins containing full-length tyrosine kinase domain s. NGF stimulation of HMC-1 cells induced tyrosine phosphorylation of TrkA protein, increased expression of the early response genes c-fos a nd NGF1-A, and activation of ERK-mitogen-activated protein (MAP) kinas e, results which indicate that trkA receptors in HMC-1 cells are fully functional. Highly purified populations of human lung mast cells expr essed mRNAs for trkA, trkB and trkC, whereas preparations of human umb ilical cord blood-derived mast cells expressed mRNAs for trkA and trkC , but not trkB. Moreover, preparations of human umbilical cord blood-d erived immature mast cells not only expressed mRNA transcript and prot ein for TrkA, but exhibited significantly higher numbers of chymase-po sitive cells after the addition of NGF to their culture medium for 3 w eeks. In addition, HMC-1 cells expressed mRNAs for NGF, brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT3), the cognate liga nds for TrkA, TrkB, and TrkC, whereas NGF and BDNF transcripts were de tectable in human umbilical cord blood mast cell preparations, Taken t ogether, our findings show that human mast cells express a functional TrkA receptor tyrosine kinase and indicate that NGF may be able to pro mote certain aspects of mast cell development and/or maturation in hum ans. Our studies also raise the possibility that human mast cells may represent a potential source for neurotrophins. (C) 1997 by The Americ an Society of Hematology.