Nerve growth factor (
NGF) can influence mast cell development and function 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 lacked p75
mRNA, they expressed transcripts for the exon-lacking splice variant of trkA (trkAI), truncated trkB (trkB.T1), and truncated trkC. By flow cytometry, HMC-1 cells exhibited expression of TrkA, TrkB, and
TrkC receptor proteins containing full-length
tyrosine kinase domains.
NGF stimulation of HMC-1 cells induced
tyrosine phosphorylation of TrkA
protein, increased expression of the early response genes c-fos and NGF1-A, and activation of ERK-
mitogen-activated
protein (MAP)
kinase, results which indicate that TrkA receptors in HMC-1 cells are fully functional. Highly purified populations of human lung mast cells expressed mRNAs for trkA, trkB and trkC, whereas preparations of human umbilical cord blood-derived mast cells expressed mRNAs for trkA and trkC, but not trkB. Moreover, preparations of human umbilical cord blood-derived immature mast cells not only expressed
mRNA transcript and
protein for TrkA, but exhibited significantly higher numbers of
chymase-positive cells after the addition of
NGF to their culture medium for 3 weeks. In addition, HMC-1 cells expressed mRNAs for
NGF,
brain-derived neurotrophic factor (
BDNF), and neurotrophin-3 (NT-3), the cognate
ligands for TrkA, TrkB, and TrkC, whereas
NGF and
BDNF transcripts were detectable in human umbilical cord blood mast cell preparations. Taken together, our findings show that human mast cells express a functional
TrkA receptor tyrosine kinase and indicate that
NGF may be able to promote certain aspects of mast cell development and/or maturation in humans. Our studies also raise the possibility that human mast cells may represent a potential source for
neurotrophins.