Stat5a Is Essential for the Proliferation and Survival of Murine Mast Cells

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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.