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The Journal of Immunology, 2001, 166: 4672-4677.
Copyright © 2001 by The American Association of Immunologists

An Increase in Circulating Mast Cell Colony-Forming Cells in Asthma1

Hadija Hemed Mwamtemi*, Kenichi Koike2,*,{ddagger}, Tatsuya Kinoshita*, Susumu Ito§, Shuichi Ishida*, Yozo Nakazawa*, Yumi Kurokawa*, Koji Shinozaki*, Kazuo Sakashita*, Kouichi Takeuchi*, Masaaki Shiohara*, Takehiko Kamijo*, Yozo Yasui*, Akira Ishiguro{dagger}{dagger}, Yoshifumi Kawano||, Kiyoshi Kitano{dagger}, Hiroshi Miyazaki#, Takashi Kato#, Shozo Sakuma{dagger}{dagger},{dagger}{dagger} and Atsushi Komiyama*

* Department of Pediatrics and {dagger} Second Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Japan; {ddagger} Shinshu University Graduate School of Medicine, Institute of Organ Transplants, Reconstructive Medicine and Tissue Engineering, Matsumoto, Japan; § Blood Transfusion Service, Shinshu University Hospital, Matsumoto, Japan; Department of Pediatrics, Mizonokuchi Hospital, Teikyo University School of Medicine, Kawasaki, Japan; || Department of Pediatrics, University of Tokushima, Tokushima, Japan; # Pharmaceutical Research Laboratory, Kirin Brewery Co. Ltd., Takasaki, Japan; and ** {dagger}{dagger} Medical Biology Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan

We compared a potential to generate mast cells among various sources of CD34+ peripheral blood (PB) cells in the presence of stem cell factor (SCF) with or without thrombopoietin (TPO), using a serum-deprived liquid culture system. From the time course of relative numbers of tryptase-positive and chymase-positive cells in the cultured cells grown by CD34+ PB cells of nonasthmatic healthy individuals treated with G-CSF, TPO appears to potentiate the SCF-dependent growth of mast cells without influencing the differentiation into mast cell lineage. CD34+ PB cells from asthmatic patients in a stable condition generated significantly more mast cells under stimulation with SCF alone or SCF+TPO at 6 wk of culture than did steady-state CD34+ PB cells of normal controls. Single-cell culture studies showed a substantial difference in the number of SCF-responsive or SCF+TPO-responsive mast cell progenitors in CD34+ PB cells between the two groups. In the presence of TPO, CD34+ PB cells from asthmatic children could respond to a suboptimal concentration of SCF to a greater extent, compared with the values obtained by those of normal controls. Six-week cultured mast cells of asthmatic subjects had maturation properties (intracellular histamine content and tryptase/chymase enzymatic activities) similar to those derived from mobilized CD34+ PB cells of nonasthmatic subjects. An increase in a potential of circulating hemopoietic progenitors to differentiate into mast cell lineage may contribute to the recruitment of mast cells toward sites of asthmatic mucosal inflammation.




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