Journal of Clinical Immunology

, Volume 21, Issue 3, pp 171–174

Human Mast Cell Apoptosis Is Regulated Through Bcl-2 and Bcl-XL

  • Yoseph A. Mekori
  • Alasdair M. Gilfillan
  • Cem Akin
  • Karin Hartmann
  • Dean D. Metcalfe
Article

DOI: 10.1023/A:1011083031272

Cite this article as:
Mekori, Y.A., Gilfillan, A.M., Akin, C. et al. J Clin Immunol (2001) 21: 171. doi:10.1023/A:1011083031272

Abstract

It is well established that human mast cell proliferation and maturation are regulated by kit ligand (stem cell factor). Little is known, however, about how these two processes are negatively regulated and thus, how mast cell number is controlled in normal and pathologic conditions. We therefore first hypothesized that SCF-dependent human mast cells would undergo programmed cell death (apoptosis) on removal of SCF as has been shown for growth factor-dependent rodent mast cells. We then examined whether SCF acts as a survival factor through the regulation of the bcl-2 family of apoptosis-regulatory genes. As hypothesized, elimination of SCF from primary peripheral blood-derived human mast cell cultures resulted in a significant apoptotic process. During apoptosis, down-regulation of the two apoptosis-regulatory proteins Bcl-2 and Bcl-XLwas observed. Moreover, a deregulated expression of these two proteins was found in two human mast cell lines which are SCF-independent. Thus, SCF functions as a survival factor by repressing apoptosis of human mast cells through Bcl-2 and Bcl-XL. Deregulated expression of these antiapoptotic proteins may contribute to proliferation and accumulation of mast cells in certain forms of systemic mast cell disorders.

Apoptosis Bcl-2 Bcl-X c-kit mast cell 

Copyright information

© Plenum Publishing Corporation 2001

Authors and Affiliations

  • Yoseph A. Mekori
    • 1
  • Alasdair M. Gilfillan
    • 2
  • Cem Akin
    • 2
  • Karin Hartmann
    • 2
  • Dean D. Metcalfe
    • 2
  1. 1.Department of Medicine Meir General Hospital, Kfar-Saba and Sackler School of MedicineTel-Aviv UniversityIsrael
  2. 2.Laboratory of Allergic Diseases, National Institute of Allergy and Infectious DiseasesNational Institutes of HealthBethesda

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