Immune Netw.  2002 Mar;2(1):53-59. 10.4110/in.2002.2.1.53.

Increased Expression of Fas Antigen and Apoptosis in Aplastic Anemia Bone Marrow Cells

• Won JH
• Lee NS
• Kim SJ
• Cheong HJ
• Lee KT
• Park SK
• Baick SH
• Kim SI
• Hong DS
• Park HS

• KMID: 1571393
• DOI: http://doi.org/10.4110/in.2002.2.1.53

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.

Keyword

Fas antigen; apoptosis; IFN-gamma; aplastic anemia

MeSH Terms

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
Antigens, CD95
Caspase 3
Chemokine CCL3
Cytokines
Interferons
Tumor Necrosis Factor-alpha