Human mast cell apoptosis is regulated through Bcl-2 and Bcl-X-L

Citation
Ya. Mekori et al., Human mast cell apoptosis is regulated through Bcl-2 and Bcl-X-L, J CLIN IMM, 21(3), 2001, pp. 171-174
Citations number
12
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Immunology
Journal title
JOURNAL OF CLINICAL IMMUNOLOGY
ISSN journal
0271-9142 → ACNP
Volume
21
Issue
3
Year of publication
2001
Pages
171 - 174
Database
ISI
SICI code
0271-9142(200105)21:3<171:HMCAIR>2.0.ZU;2-Q
Abstract
It is well established that human mast cell proliferation and maturation ar e regulated by kit ligand (stem cell factor). Little is known, however, abo ut how these two processes are negatively regulated and thus, how mast cell number is controlled in normal and pathologic conditions. We therefore fir st hypothesized that SCF-dependent human mast cells would undergo programme d cell death (apoptosis) on removal of SCF as has been shown for growth fac tor-dependent rodent mast cells. We then examined whether SCF acts as a sur vival factor through the regulation of the bcl-2 family of apoptosis-regula tory genes. As hypothesized, elimination of SCF from primary peripheral blo od-derived human mast cell cultures resulted in a significant apoptotic pro cess. During apoptosis, down-regulation of the two apoptosis-regulatory pro teins Bcl-2 and Bcl-X-L was observed. Moreover, a deregulated expression of these two proteins was found in two human mast cell lines which are SCF-in dependent. Thus, SCF functions as a survival factor by repressing apoptosis of human mast cells through Bcl-2 and Bcl-X-L. Deregulated expression of t hese antiapoptotic proteins may contribute to proliferation and accumulatio n of mast cells in certain forms of systemic mast cell disorders.