Role of activin A in murine mast cells: modulation of cell growth, differentiation, and migration.
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 IC(50) 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.
Funaba
Masayuki
M
Laboratories of Nutrition and. Molecular Biology, Azabu University School of Veterinary Medicine, Sagamihara, Japan. funaba@azabu-u.ac.jp
Ikeda
Teruo
T
Ogawa
Kenji
K
Murakami
Masaru
M
Abe
Matanobu
M
D028341:Activins / Q000494:pharmacology* / Q000502:physiology; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D053818:Chymases; D004305:Dose-Response Relationship, Drug; D028322:Inhibin-beta Subunits / Q000494:pharmacology* / Q000502:physiology; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000096:biosynthesis; D012697:Serine Endopeptidases / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000502:physiology
D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; C422405:activin A; D028341:Activins; D028322:Inhibin-beta Subunits; D012697:Serine Endopeptidases; D053818:Chymases; C509230:Mcpt1 protein, mouse