International Archives of Allergy and Immunology

Original Paper

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

Ikeda K. · Nakajima H. · Suzuki K. · Watanabe N. · Kagami S.-i. · Iwamoto I.

Author affiliations

Department of Allergy and Clinical Immunology, Clinical Cell Biology, Graduate School of Medicine, Chiba University, Chiba, Japan

Related Articles for ""

Int Arch Allergy Immunol 2005;137:45–50

Log in to MyKarger to check if you already have access to this content.


Buy

  • FullText & PDF
  • Unlimited re-access via MyKarger
  • Unrestricted printing, no saving restrictions for personal use
read more

CHF 38.00 *
EUR 35.00 *
USD 39.00 *

Select

KAB

Buy a Karger Article Bundle (KAB) and profit from a discount!


If you would like to redeem your KAB credit, please log in.


Save over 20% compared to the individual article price.

Learn more

Rent/Cloud

  • Rent for 48h to view
  • Buy Cloud Access for unlimited viewing via different devices
  • Synchronizing in the ReadCube Cloud
  • Printing and saving restrictions apply

Rental: USD 8.50
Cloud: USD 20.00

Select

Subscribe

  • Access to all articles of the subscribed year(s) guaranteed for 5 years
  • Unlimited re-access via Subscriber Login or MyKarger
  • Unrestricted printing, no saving restrictions for personal use
read more

Subcription rates


Select
* The final prices may differ from the prices shown due to specifics of VAT rules.

Article / Publication Details

First-Page Preview
Abstract of Original Paper

Published online: June 03, 2005
Issue release date: June 2005

Number of Print Pages: 6
Number of Figures: 4
Number of Tables: 0

ISSN: 1018-2438 (Print)
eISSN: 1423-0097 (Online)

For additional information: https://www.karger.com/IAA

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.

© 2005 S. Karger AG, Basel




Related Articles:


References

  1. Galli SJ, Hammel I: Mast cell and basophil development. Curr Opin Hematol 1994;1:33–39.
  2. Metcalfe DD, Baram D, Mekori YA: Mast cells. Physiol Rev 1997;77:1033–1079.
  3. Lantz CS, Huff TF: Differential responsiveness of purified mouse c-kit+ mast cells and their progenitors to IL-3 and stem cell factor. J Immunol 1995;155:4024–4029.
  4. Rodewald HR, Dessing M, Dvorsak AM, Galli SJ: Identification of a committed precursor for the mast cell lineage. Science 1996;271:818–822.
  5. Lantz CS, Boesiger J, Song CH, Mach N, Kobayashi T, Mulligan RC, Nawa Y, Dranoff G, Galli SJ: Role for interleukin-3 in mast-cell and basophil development and in immunity to parasites. Nature 1998;392:90–93.
  6. Leonard WJ: STATs and cytokine specificity. Nat Med 1996;2:968–969.
  7. Leonard WJ, O’Shea JJ: Jaks and STATs: Biological implications. Annu Rev Immunol 1998;16:293–322.
  8. Nosaka T, Kawashima T, Misawa K, Ikuta K, Mui AL, Kitamura T: STAT5 as a molecular regulator of proliferation, differentiation and apoptosis in hematopoietic cells. EMBO J 1999;18:4754–4765.
  9. Lin J-X, Leonard WJ: The role of Stat5a and Stat5b in signaling by IL-2 family cytokines. Oncogene 2000;19:2566–2576.
  10. Shelburne CP, McCoy ME, Piekorz R, Sexl V, Roh KH, Jacobs-Helber SM, Gillespie SR, Bailey DP, Mirmonsef P, Mann MN, Kashyap M, Wright HV, Chong HJ, Bouton LA, Barnstein B, Ramirez CD, Bunting KD, Sawyer S, Lantz CS, Ryan JJ: Stat5 expression is critical for mast cell development and survival. Blood 2003;102:1290–1297.
  11. Liu X, Robinson GW, Wagner KU, Garrett L, Wynshaw-Boris A, Hennighausen L: Stat5a is mandatory for adult mammary gland development and lactogenesis. Genes Dev 1997;11:179–186.
  12. Ihle JN, Keller J, Oersozlan S, Henderson LE, Copeland TD, Fitch F, Prystwsky MB, Goldwasser E, Schrader JW, Palaszynski E, Dy M, Lebel B: Biological properties of homogenous interleukin 3. I. Demonstration of WEHI-3 growth-factor activity, mast cell growth factor activity, P cell-stimulating factor activity and histamine-producing factor activity. J Immunol 1983;131:282–287.
  13. Karasuyama H, Melchers F: Establishment of mouse cell lines which constitutively secrete large quantities of interleukin 2, 3, 4, or 5, using modified cDNA expression vectors. Eur J Immunol 1988;18:97–104.
  14. Nakajima H, Shores EW, Noguchi M, Leonard WJ: The common cytokine receptor γ chain plays an essential role in regulating lymphoid homeostasis. J Exp Med 1997;185:189–195.
  15. Boise LH, Gonzalez-Garcia M, Postema CE, Ding L, Lindsten T, Turka LA, Mao X, Nunez G, Thompson CB: bcl-x, a bcl-2-related gene that functions as a dominant regulator of apoptotic cell death. Cell 1993;74:597–608.
  16. Motoyama N, Wang F, Roth KA, Sawa H, Nakayama K, Nakayama K, Negishi I, Senju S, Zhang Q, Fujii S, Loh DY: Massive cell death of immature hematopoietic cells and neurons in Bcl-x-deficient mice. Science 1995;267:1506–1510.
  17. Dumon S, Santos SC, Debierre-Grockiego F, Gouilleux-Gruart V, Cocault L, Boucheron C, Mollat P, Gisselbrecht S, Gouilleux F: IL-3 dependent regulation of Bcl-xL gene expression by STAT5 in a bone marrow derived cell line. Oncogene 1999;18:4191–4199.
  18. O’Farrell AM, Ichihara M, Mui AL, Miyajima A: Signaling pathways activated in a unique mast cell line where interleukin-3 supports survival and stem cell factor is required for a proliferative response. Blood 1996;87:3655–3668.
  19. Timokhina I, Kissel H, Stella G, Besmer P: Kit signaling through PI 3-kinase and Src kinase pathways: An essential role for Rac1 and JNK activation in mast cell proliferation. EMBO J 1998;17:6250–6262.
  20. Rosa Santos SC, Dumon S, Mayeau P, Gisselbrecht S, Gouilleux F: Cooperation between STAT5 and phosphatidylinositol 3-kinase in the IL-3-dependent survival of a bone marrow derived cell line. Oncogene 2000;19:1164–1172.

Article / Publication Details

First-Page Preview
Abstract of Original Paper

Published online: June 03, 2005
Issue release date: June 2005

Number of Print Pages: 6
Number of Figures: 4
Number of Tables: 0

ISSN: 1018-2438 (Print)
eISSN: 1423-0097 (Online)

For additional information: https://www.karger.com/IAA


Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
TOP