Increased Expression of Fas Antigen and Apoptosis in Aplastic Anemia Bone Marrow Cells
Immune Network
;
: 53-59, 2002.
Artigo
em Coreano
| WPRIM
| ID: wpr-228525
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.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Doadores de Tecidos
/
Medula Óssea
/
Células da Medula Óssea
/
Células-Tronco Hematopoéticas
/
Transdução de Sinais
/
Citocinas
/
Interferons
/
Fator de Necrose Tumoral alfa
/
Apoptose
/
Receptor fas
Limite:
Humanos
Idioma:
Coreano
Revista:
Immune Network
Ano de publicação:
2002
Tipo de documento:
Artigo
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