Journal of Leukocyte Biology Myeloid cells, immune suppression, tumor immunology
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A more recent version of this article appeared on June 1, 2003

Published online before print May 22, 2003
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© 2003 by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0103012

Received for publication January 9, 2003.
Revised February 23, 2003.
Accepted for publication February 26, 2003.

Article

Role of activin A in murine mast cells: modulation of cell growth, differentiation, and migration

Masayuki Funaba *@, Teruo Ikeda {dagger}, Kenji Ogawa {ddagger}, Masaru Murakami §, and Matanobu Abe *

Laboratories of *Nutrition and §Molecular Biology, Azabu University School of Veterinary Medicine, and {dagger}Azabu University Research Institute of Biosciences, Sagamihara, Japan; and {ddagger}Laboratory of Cellular Biochemistry, RIKEN, Wako, Japan

@ To whom correspondence should be addressed. E-mail: funaba{at}azabu-u.ac.jp.


  Abstract

Activins, members of the transforming growth factor-{beta} (TGF-{beta}) superfamily, are potent growth and differentiation factors. Our previous studies revealed that activin A, a homodimer of inhibin/activin {beta}A, was induced in mast cells and peritoneal macrophages in response to their activation. In the present study, we examined the roles of activin A in murine bone marrow-derived, cultured mast cell progenitors (BMCMCs), which expressed gene transcripts for molecules involved in activin signaling, suggesting that BMCMCs could be target cells of activin A. Treatment of activin A inhibited 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide uptake into BMCMCs in a dose-dependent manner. The IC50 concentration was 2.1 nM, which was less potent than 185 pM TGF-{beta}1. Activin A treatment caused morphological changes toward the differentiated cells at 2 nM and up-regulated mRNA of mouse mast cell protease-1 (mMCP-1), a marker enzyme of mature mucosal mast cells, at 1 nM. Activin A also showed activity in inducing migration of BMCMCs; the optimal concentration for maximal migration was 10 PM, which was much lower than the concentrations to inhibit cell growth and to activate the mMCP-1 gene. Taking the present results together with our previous results, it is suggested that activin A secreted from activated immune cells recruits mast cell progenitors to sites of inflammation and that with increasing activin A concentration, the progenitors differentiate into mature mast cells. Thus, activin A may positively regulate the functions of mast cells as effector cells of the immune system.

Key Words: mouse mast cell protease-1 • transforming growth factor-{beta} • dose-dependent activity • immune response






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Copyright © 2003 by the Society for Leukocyte Biology.