Increased Expression of Fas Antigen and Apoptosis in Aplastic Anemia Bone Marrow Cells.
- Author:
Jong Ho WON
1
;
Nam Su LEE
;
Sook Ja KIM
;
Hee Jeong CHEONG
;
Kyu Taeg LEE
;
Seung Kyu PARK
;
Seung Ho BAICK
;
Sung Il KIM
;
Dae Sik HONG
;
Hee Sook PARK
Author Information
- Publication Type:Original Article
- Keywords: Fas antigen; apoptosis; IFN-gamma; aplastic anemia
- MeSH: Anemia, Aplastic*; Antigens, CD95*; Apoptosis*; Bone Marrow Cells*; Bone Marrow*; Caspase 3; Chemokine CCL3; Cytokines; Hematopoietic Stem Cells; Humans; Immunity, Cellular; Interferons; Signal Transduction; Tissue Donors; Tumor Necrosis Factor-alpha
- From:Immune Network 2002;2(1):53-59
- CountryRepublic of Korea
- Language:Korean
- Abstract: BACKGROUND: Clinical observations and laboratory studies have supported an immune basis for most acquired aplastic anemias, with the majority of patients responding to immunosuppressive therapy. Fas, a member of the tumor necrosis factor (TNF) receptor superfamily is a critical downregulator of cellular immune responses. Proinflammatory cytokines like interferon gamma (IFN-gamma) and TNF-alpha can induce Fas expression and render hematopoietic progenitor cells susceptible to Fas-induced growth suppression and apoptosis. METHODS: In order to investigate the involvement of apoptosis in the pathogenesis of aplastic anemia (AA), we measured the expression of Fas antigen and caspase-3 on bone marrow (BM) mononuclear cells (MNCs) of AA in the presence or absence of IFN-gamma, TNF-alpha, or macrophage inflammatory protein 1-alpha (MIP-1alpha). RESULTS: We confirmed that AA BM MNCs were more apoptotic and highly expressed Fas antigen than normal donors. Stimulation by IFN-gamma, TNF-alpha, or MIP-1alpha increased Fas antigen and caspase-3 expression in AA BM MNCs than BM MNCs of normal donors. Anti-Fas monoclonal antibody enhanced IFN-gamma, TNF-alpha, or MIP-1alpha mediated caspase-3 expression in BM MNCs of normal donors. Among these three cytokines, IFN-gamma enhanced apoptosis most strongly via Fas-caspase-3 pathway. CONCLUSION: These results suggest that Fas signal pathway may play a role in the pathophysiology of aplastic anemia and negative hematopoietic regulators like IFN-gamma can induce apoptosis of bone marrow progenitors in part by Fas induction.
