Natural killer cell-dependent apoptosis of peripheral murine hematopoietic progenitor cells in response to Fas cross-linking: involvement of tumor necrosis factor-alpha.
Blood
; 97(10): 3069-74, 2001 May 15.
Article
en En
| MEDLINE
| ID: mdl-11342432
ABSTRACT
Recently, a marked extramedullary myelopoiesis in Fas/CD95- or FasL/CD95L-deficient mice has been reported. In the present in vitro study, the mechanisms underlying Fas-induced apoptosis of normal peripheral colony-forming unit-C (CFU-C) progenitors in the spleen were analyzed. Surprisingly, it was found that clonogenic progenitors were protected from gammaIFN plus Fas-induced programmed cell death when Lin(+) cells were removed from cultured splenocytes. The cells that rendered CFU-C sensitive to the activation of the Fas pathway did not belong to the T or the myelocytic-monocytic lineage but comprised a non-B-cell subset expressing the activation marker B220. Among CD19(-) B220(+) splenocytes, nearly half were natural killer (NK) 1.1(+) cells whose in vivo depletion or deficiency in RAG2-gamma(c)(-/-) mice abrogated the effect of Fas cross-linking. NK cells exerted their accessory function, at least in part, through tumor necrosis factor-alpha (TNF-alpha), which they readily produced during pretreatment with the anti-Fas/CD95 monoclonal antibody and IFN-gamma and whose addition could compensate for the loss of sensitivity. In conclusion, this study provides evidence that peripheral clonogenic progenitors are not directly responsive to Fas cross-linking, even in the presence of IFN-gamma, but require NK cells as a source of TNF-alpha to make them susceptible to this death pathway.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Células Madre Hematopoyéticas
/
Células Asesinas Naturales
/
Factor de Necrosis Tumoral alfa
/
Apoptosis
/
Receptor fas
Límite:
Animals
Idioma:
En
Revista:
Blood
Año:
2001
Tipo del documento:
Article
País de afiliación:
Francia