Published online before print May 22, 2003
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* Laboratories of Nutrition and
Molecular Biology, Azabu University School of Veterinary Medicine, and
Azabu University Research Institute of Biosciences, Sagamihara, Japan; and
Laboratory of Cellular Biochemistry, RIKEN, Wako, Japan
Correspondence: Masayuki Funaba, Ph.D., Laboratory of Nutrition, Azabu University School of Veterinary Medicine, 1-17-71 Fuchinobe, Sagamihara 229-8501, Japan. E-mail: funaba{at}azabu-u.ac.jp
Activins, members of the transforming growth factor-ß (TGF-ß) superfamily, are potent growth and differentiation factors. Our previous studies revealed that activin A, a homodimer of inhibin/activin ßA, 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-ß1. 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-ß • dose-dependent activity • immune response
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