title: Stat5a is essential for the proliferation and survival of murine mast cells.
abstract: The regulatory role of signal transducer and activator of transcription (Stat) 5a in the proliferation and survival of mast cells was determined using Stat5a-deficient (Stat5a(-/-)) mice. First, although the mast cells in Stat5a(-/-) mice were morphologically indistinguishable from those in wild-type (WT) mice, the number of peritoneal mast cells was significantly decreased in Stat5a(-/-) mice as compared with that in WT mice. Furthermore, the interleukin-3 (IL-3)-dependent development of bone marrow-derived mast cells (BMMCs) was markedly decreased in Stat5a(-/-) mice. Second, IL-3-induced but not stem cell factor (SCF)-induced proliferation of BMMCs was significantly diminished in Stat5a(-/-) mice as compared with that in WT mice. Moreover, survival rates of both peritoneal mast cells and BMMCs were significantly decreased with increased apoptotic cells in Stat5a(-/-) mice as compared with those in WT mice. Finally, mRNA of Bcl-x(L) was induced after IL-3 stimulation in WT BMMCs but not in Stat5a(-/-) BMMCs, which may account for the accelerated apoptosis in Stat5a(-/-) mast cells. These results indicate that Stat5a plays an important role in mast cell development, proliferation, and survival.
authors.affiliation: Department of Allergy and Clinical Immunology, Clinical Cell Biology, Graduate School of Medicine, Chiba University, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Ikeda
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakajima
authors.forename: Kotaro
authors.initials: K
authors.lastname: Suzuki
authors.forename: Norihiko
authors.initials: N
authors.lastname: Watanabe
authors.forename: Shin-ichiro
authors.initials: S
authors.lastname: Kagami
authors.forename: Itsuo
authors.initials: I
authors.lastname: Iwamoto
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D048708:Cell Growth Processes / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D007073:Immunoglobulin E / Q000276:immunology; D007377:Interleukin-3 / Q000494:pharmacology; D008407:Mast Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008894:Milk Proteins / Q000235:genetics / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050799:STAT5 Transcription Factor; D013047:Specific Pathogen-Free Organisms; D019089:Stem Cell Factor / Q000276:immunology; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics / Q000276:immunology / Q000502:physiology*
chemical_list: D004268:DNA-Binding Proteins; D007377:Interleukin-3; D008894:Milk Proteins; D050799:STAT5 Transcription Factor; C494093:Stat5a protein, mouse; D019089:Stem Cell Factor; D015534:Trans-Activators; D007073:Immunoglobulin E