PMID- 9292513 OWN - NLM STAT- MEDLINE DCOM- 19970930 LR - 20210216 IS - 0006-4971 (Print) IS - 0006-4971 (Linking) VI - 90 IP - 5 DP - 1997 Sep 1 TI - Expression of functional TrkA receptor tyrosine kinase in the HMC-1 human mast cell line and in human mast cells. PG - 1807-20 AB - 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. FAU - Tam, S Y AU - Tam SY AD - Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA. FAU - Tsai, M AU - Tsai M FAU - Yamaguchi, M AU - Yamaguchi M FAU - Yano, K AU - Yano K FAU - Butterfield, J H AU - Butterfield JH FAU - Galli, S J AU - Galli SJ LA - eng GR - AI/CA-23990/AI/NIAID NIH HHS/United States GR - CA/AI-72074/CA/NCI NIH HHS/United States GR - HL-56383/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (Nerve Growth Factors) RN - 0 (Proto-Oncogene Proteins) RN - 0 (RNA, Messenger) RN - 0 (Receptors, Nerve Growth Factor) RN - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases) RN - EC 2.7.10.1 (Receptor, trkA) SB - IM MH - Cell Line MH - Enzyme Activation MH - Flow Cytometry MH - Humans MH - Kinetics MH - Mast Cells/*metabolism MH - Nerve Growth Factors/*pharmacology MH - Proto-Oncogene Proteins/*biosynthesis/genetics MH - RNA, Messenger/biosynthesis/genetics MH - Receptor Protein-Tyrosine Kinases/*biosynthesis/genetics MH - Receptor, trkA MH - Receptors, Nerve Growth Factor/*biosynthesis/genetics EDAT- 1997/09/18 00:00 MHDA- 1997/09/18 00:01 CRDT- 1997/09/18 00:00 PHST- 1997/09/18 00:00 [pubmed] PHST- 1997/09/18 00:01 [medline] PHST- 1997/09/18 00:00 [entrez] AID - S0006-4971(20)58787-9 [pii] PST - ppublish SO - Blood. 1997 Sep 1;90(5):1807-20.