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Blood, Vol. 94 No. 2 (July 15), 1999:
pp. 496-508
Interleukin-6 Directly Modulates Stem Cell Factor-Dependent
Development of Human Mast Cells Derived From CD34+
Cord Blood Cells
Tatsuya Kinoshita,
Nobukuni Sawai,
Eiko Hidaka,
Tetsuji Yamashita, and
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.
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.
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