Human mast cell apoptosis is regulated through Bcl-2 and Bcl-XL

被引:70
作者
Mekori, YA
Gilfillan, AM
Akin, C
Hartmann, K
Metcalfe, DD
机构
[1] Meir Hosp, Dept Med, Kefar Sava, Israel
[2] Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel
[3] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA
关键词
apoptosis; Bcl-2; Bcl-X; c-kit; mast cell;
D O I
10.1023/A:1011083031272
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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-X-L 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-X-L. Deregulated expression of these antiapoptotic proteins may contribute to proliferation and accumulation of mast cells in certain forms of systemic mast cell disorders.
引用
收藏
页码:171 / 174
页数:4
相关论文
共 13 条
[1]  
Cerveró C, 1999, AM J HEMATOL, V60, P191, DOI 10.1002/(SICI)1096-8652(199903)60:3<191::AID-AJH4>3.0.CO
[2]  
2-Y
[3]   REGULATION OF LYMPHOCYTE SURVIVAL BY THE BCL-2 GENE FAMILY [J].
CORY, S .
ANNUAL REVIEW OF IMMUNOLOGY, 1995, 13 :513-543
[4]   Glucocorticoids decrease tissue mast cell number by reducing the production of the c-kit ligand, stem cell factor, by resident cells - In vitro and in vivo evidence in murine systems [J].
Finotto, S ;
Mekori, YA ;
Metcalfe, DD .
JOURNAL OF CLINICAL INVESTIGATION, 1997, 99 (07) :1721-1728
[5]   IDENTIFICATION OF MUTATIONS IN THE CODING SEQUENCE OF THE PROTOONCOGENE C-KIT IN A HUMAN MAST-CELL LEUKEMIA-CELL LINE CAUSING LIGAND-INDEPENDENT ACTIVATION OF C-KIT PRODUCT [J].
FURITSU, T ;
TSUJIMURA, T ;
TONO, T ;
IKEDA, H ;
KITAYAMA, H ;
KOSHIMIZU, U ;
SUGAHARA, H ;
BUTTERFIELD, JH ;
ASHMAN, LK ;
KANAYAMA, Y ;
MATSUZAWA, Y ;
KITAMURA, Y ;
KANAKURA, Y .
JOURNAL OF CLINICAL INVESTIGATION, 1993, 92 (04) :1736-1744
[6]   A role for Bax in the regulation of apoptosis in mouse mast cells [J].
Maurer, M ;
Tsai, M ;
Metz, M ;
Fish, S ;
Korsmeyer, SJ ;
Galli, SJ .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2000, 114 (06) :1205-1206
[7]  
MCKORI YA, 1999, SIGNAL TRANSDUCTION, P85
[8]   Characterization of a mast cell line that lacks the extracellular domain of membrane c-kit [J].
Mekori, YA ;
Oh, CK ;
Dastych, J ;
Goff, JP ;
Adachi, S ;
Bianchine, PJ ;
Worobec, A ;
Semere, T ;
Pierce, JH ;
Metcalfe, DD .
IMMUNOLOGY, 1997, 90 (04) :518-525
[9]  
ROTTEM M, 1994, BLOOD, V84, P2489
[10]   The expression of Bcl-x is downregulated during differentiation of human hematopoietic progenitor cells along the granulocyte but not the monocyte/macrophage lineage [J].
Sanz, C ;
Benito, A ;
Silva, M ;
Albella, B ;
Richard, C ;
Segovia, JC ;
Insunza, A ;
Bueren, JA ;
FernandezLuna, JL .
BLOOD, 1997, 89 (09) :3199-3204