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Prepublished online as a Blood First Edition Paper on April 24, 2003; DOI 10.1182/blood-2002-11-3490.

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Blood, 15 August 2003, Vol. 102, No. 4, pp. 1290-1297

HEMATOPOIESIS

Stat5 expression is critical for mast cell development and survival

Christopher P. Shelburne, Margaret E. McCoy, Roland Piekorz, Veronica Sexl, Kwan-Ho Roh, Sarah M. Jacobs-Helber, Sheila R. Gillespie, Daniel P. Bailey, Paria Mirmonsef, Meredith N. Mann, Mohit Kashyap, Harry V. Wright, Hey Jin Chong, L. Andrew Bouton, Brian Barnstein, Carlos D. Ramirez, Kevin D. Bunting, Steven Sawyer, Chris S. Lantz, and John J. Ryan

From the Department of Biology, Virginia Commonwealth University, Richmond, VA; the Department of Biology, James Madison University, Harrisonburg, VA; the Department of Biochemistry, St Jude Children's Research Hospital, Memphis, TN; the Departments of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA; the Department of Hematopoiesis, Jerome H. Holland Laboratory for the Biomedical Sciences, Rockville, MD; and The George Washington University, Washington, DC.

Interleukin-3 (IL-3) and stem cell factor (SCF) are important mast cell growth and differentiation factors. Since both cytokines activate the transcription factor signal transducer and activator of transcription 5 (Stat5), a known regulator of proliferation and survival, we investigated the effects of Stat5 deficiency on mast cell development and survival. Bone marrow–derived mast cell (BMMC) populations cultured from Stat5A/B-deficient mice survived in IL-3 + SCF, but not in either cytokine alone. These cells demonstrated reduced expression of Bcl-2, Bcl-x(L), cyclin A2, and cyclin B1, with increased apoptosis and delayed cell cycle progression during IL-3 or SCF culture. Finally, the absence of Stat5 resulted in loss of in vivo mast cell development, as judged by assessments of Stat5-deficient mice and transplantation of Stat5-deficient bone marrow cells to mast cell-deficient recipient mice. These results indicate that Stat5A and Stat5B are critical regulators of in vitro and in vivo mast cell development and survival.


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