Interleukin-6 Directly Modulates Stem Cell Factor-Dependent Development of Human Mast Cells Derived From CD34+Cord Blood Cells

  • Tatsuya Kinoshita
    From the Department of Pediatrics, Shinshu University School of Medicine, and Central Clinical Laboratories, Shinshu University Hospital, Matsumoto, Japan; and Research & Development, Mitsubishi Kagaku Bio-Clinical Laboratories, Inc, Tokyo, Japan.
  • Nobukuni Sawai
    From the Department of Pediatrics, Shinshu University School of Medicine, and Central Clinical Laboratories, Shinshu University Hospital, Matsumoto, Japan; and Research & Development, Mitsubishi Kagaku Bio-Clinical Laboratories, Inc, Tokyo, Japan.
  • Eiko Hidaka
    From the Department of Pediatrics, Shinshu University School of Medicine, and Central Clinical Laboratories, Shinshu University Hospital, Matsumoto, Japan; and Research & Development, Mitsubishi Kagaku Bio-Clinical Laboratories, Inc, Tokyo, Japan.
  • Tetsuji Yamashita
    From the Department of Pediatrics, Shinshu University School of Medicine, and Central Clinical Laboratories, Shinshu University Hospital, Matsumoto, Japan; and Research & Development, Mitsubishi Kagaku Bio-Clinical Laboratories, Inc, Tokyo, Japan.
  • Kenichi Koike
    From the Department of Pediatrics, Shinshu University School of Medicine, and Central Clinical Laboratories, Shinshu University Hospital, Matsumoto, Japan; and Research & Development, Mitsubishi Kagaku Bio-Clinical Laboratories, Inc, Tokyo, Japan.

Bibliographic Information

Published
1999-07-15
DOI
  • 10.1182/blood.v94.2.496
  • 10.1182/blood.v94.2.496.414k19_496_508
Publisher
American Society of Hematology

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Description

<jats:title>Abstract</jats:title><jats:p>In the present study, we attempted to clarify the effects of interleukin-6 (IL-6) on the growth and properties of human mast cells using cultured mast cells selectively generated by stem cell factor (SCF) from CD34+ cord blood cells. The addition of IL-6 to cultures containing mast cells resulted in a substantial reduction of the number of progenies grown by SCF in the liquid culture. This IL-6–mediated inhibition of mast cell growth may be due in part to the suppression at the precursor level, according to the results of a clonal cell culture assay. Moreover, a flow cytometric analysis showed that the cultured mast cells grown in the presence of SCF+IL-6 had decreased c-kit expression. The exposure of cultured mast cells to SCF+IL-6 also caused substantial increases in the cell size, frequency of chymase-positive cells, and intracellular histamine level compared with the values obtained with SCF alone. The flow cytometric analysis showed low but significant levels of expression of IL-6 receptor (IL-6R) and gp130 on the cultured mast cells grown with SCF. The addition of either anti–IL-6R antibody or anti-gp130 antibody abrogated the biological functions of IL-6. Although IL-4 exerted an effect similar to that of IL-6 on the cultured mast cells under stimulation with SCF, the results of comparative experiments suggest that the two cytokines use different regulatory mechanisms. Taken together, the present findings suggest that IL-6 modulates SCF-dependent human mast cell development directly via an IL-6R-gp130 system.</jats:p>

Journal

  • Blood

    Blood 94 (2), 496-508, 1999-07-15

    American Society of Hematology

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