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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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-XL was 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.

Original languageEnglish
Pages (from-to)171-174
Number of pages4
JournalJournal of Clinical Immunology
Volume21
Issue number3
DOIs
StatePublished - 2001
Externally publishedYes

Funding

FundersFunder number
National Institute of Allergy and Infectious DiseasesZIAAI000513

    Keywords

    • Apoptosis
    • Bcl-2
    • Bcl-X
    • C-kit
    • Mast cell

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