Stem cell factor-induced downregulation of c-kit in human lung mast cells and HMC-1 mast cells

M. Baghestanian, H. Agis, D. Bevec, H. C. Bankl, R. Hofbauer, H. G. Kress, J. H. Butterfield, M. R. Muller, L. K. Ashman, W. Fureder, M. Willheim, K. Lechner, P. Valent

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

Recent data suggest that local overexpression of the tissue-hormone c-kit ligand (stem cell factor [SCF]) is associated with accumulation of mast cells (MCs) and a decrease in expression of c-kit in the accumulated MCs. In the present study, the effects of recombinant human (rh) SCF on expression of c-kit mRNA and c-kit protein in isolated human MCs and a human mast cell line, HMC-1, were analyzed. Incubation of isolated lung MC with rhSCF (100 ng/mL) for 120 minutes resulted in decreased expression of c-kit mRNA (optical density [OD], control: 100% vs. rhSCF: 37%). Almost identical results were obtained with HMC-1 cells (OD, control: 100% vs. rhSCF: 40 to 45%). As assessed by flow cytometry and monoclonal antibodies (mAbs) to c-kit, the SCF-induced decrease of c-kit mRNA in HMC-1 was associated with a substantial decrease in surface expression of c-kit (MFI, control: 100 ± 21%, vs. MFI in cells incubated with rhSCF [100 ng/mL at 37°C for 12 hours]: 8 ± 2%, vs. MFI in cells incubated with rhSCF, 100 ng/mL, at 4°C: 34 ± 3%). The effects of rhSCF on c-kit expression in HMC-1 cells were dose- and time-dependent with maximum effects observed with 10-100 ng/mL of rhSCF after 4 to 12 hours. The SCF-dependent loss of c-kit was also accompanied by a decreased chemotactic response to rhSCF (control: 100%; rhSCF: 71 ± 2%). This study shows that exposure of human lung MC and HMC-1 cells to recombinant SCF results in downregulation of c-kit mRNA and surface c-kit expression. These data may explain the partial loss of c-kit on MCs in areas of SCF overexpression.

Original languageEnglish (US)
Pages (from-to)1377-1386
Number of pages10
JournalExperimental Hematology
Volume24
Issue number12
StatePublished - 1996

Keywords

  • Chemotaxis
  • Mast cells
  • Stem cell factor
  • c-kit

ASJC Scopus subject areas

  • Molecular Biology
  • Hematology
  • Genetics
  • Cell Biology
  • Cancer Research

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