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Blood, Vol. 95 No. 9 (May 1), 2000:
pp. 2821-2828
Retinoic acid is a negative regulator for the differentiation of
cord blood-derived human mast cell progenitors
Tatsuya Kinoshita,
Kenichi Koike,
Hadija
Hemed Mwamtemi,
Susumu Ito,
Shuichi Ishida,
Yozo Nakazawa,
Yumi Kurokawa,
Kazuo Sakashita,
Tsukasa Higuchi,
Kouichi Takeuchi,
Nobukuni Sawai,
Masaaki Shiohara,
Takehiko Kamijo,
Shigeyuki Kawa,
Tetsuji Yamashita, and
Atsushi Komiyama
From the Department of Pediatrics, Second Department of Internal
Medicine, Shinshu University School of Medicine, Matsumoto; Blood
Transfusion Service, Shinshu University Hospital, Matsumoto; Research
and Development, Mitsubishi Kagaku Bio-Clinical Laboratories, Inc,
Tokyo, Japan.
We examined the effects of retinoids on the human mast cell
development using a serum-deprived culture system. When 10-week cultured mast cells derived from CD34+ cord blood cells
were used as target cells, both all-trans retinoic acid (ATRA)
and 9-cis RA inhibited the progeny generation under stimulation
with stem cell factor (SCF) in a dose-dependent manner (the number of
progeny grown by SCF plus RA at 10 7 mol/L was one tenth
of the value obtained by SCF alone). The early steps in mast cell
development appear to be less sensitive to RA according to the single
CD34+c-kit+ cord blood cell culture study.
The optimal concentration of RAs also reduced the histamine
concentration in the cultured mast cells (3.00 ± 0.47 pg per cell
in SCF alone, 1.44 ± 0.18 pg per cell in SCF+ATRA, and
1.41 ± 0.10 pg per cell in SCF+9-cis RA). RT-PCR
analyses showed the expression of RAR , RAR , RXR , and RXR
messenger ribonucleic acid (mRNA) in 10-week cultured mast cells. The
addition of an RAR-selective agonist at 10 10 mol/L to
10 7 mol/L decreased the number of mast cells grown in
SCF, whereas an RXR-selective agonist at up to 10 8 mol/L
was inactive. Among RAR subtype selective retinoids used at
10 9 mol/L to 10 7 mol/L, only the RAR
agonist was equivalent to ATRA at 10 7 mol/L in its
ability to inhibit mast cell growth. Conversely, the addition of excess
concentrations of a RAR antagonist profoundly counteracted the
retinoid-mediated suppressive effects. These results suggest that RA
inhibits SCF-dependent differentiation of human mast cell progenitors
through a specific receptor.

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