Stat5 expression is critical for mast cell development and survival.
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.
Shelburne
Christopher P
CP
Department of Biology, Virginia Commonwealth University, Richmond, VA 23284-2012, USA.
McCoy
Margaret E
ME
Piekorz
Roland
R
Sexl
Veronica
V
Roh
Kwan-Ho
KH
Jacobs-Helber
Sarah M
SM
Gillespie
Sheila R
SR
Bailey
Daniel P
DP
Mirmonsef
Paria
P
Mann
Meredith N
MN
Kashyap
Mohit
M
Wright
Harry V
HV
Chong
Hey Jin
HJ
Bouton
L Andrew
LA
Barnstein
Brian
B
Ramirez
Carlos D
CD
Bunting
Kevin D
KD
Sawyer
Steven
S
Lantz
Chris S
CS
Ryan
John J
JJ
D000818:Animals; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D016213:Cyclins / Q000096:biosynthesis / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000172:deficiency / Q000502:physiology*; D004789:Enzyme Activation / Q000235:genetics; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D008407:Mast Cells / Q000166:cytology* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008894:Milk Proteins; D008928:Mitochondria / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D050799:STAT5 Transcription Factor; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D019089:Stem Cell Factor / Q000494:pharmacology; D015534:Trans-Activators / Q000096:biosynthesis / Q000172:deficiency / Q000502:physiology*; D025521:Tumor Suppressor Proteins; D015854:Up-Regulation
D016213:Cyclins; D004268:DNA-Binding Proteins; D007377:Interleukin-3; D008894:Milk Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins; D050799:STAT5 Transcription Factor; C494092:STAT5A protein, human; C494095:STAT5B protein, human; C494093:Stat5a protein, mouse; C494096:Stat5b protein, mouse; D019089:Stem Cell Factor; D015534:Trans-Activators; D025521:Tumor Suppressor Proteins; D020169:Caspases