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Un mutante no secretor de la superficie celular del factor de necrosis tumoral (TNF) mata por contacto de célula a
1Department of Molecular Biology, Cetus Corporation, Emeryville, California 94608.
Cell
|October 19, 1990
Resumen
El factor de necrosis tumoral (TNF) tiene dos formas: secretoria y transmembrana. La forma transmembrana del TNF mata directamente a las células diana a través del contacto celular, a diferencia de la forma secretora.
Área de la Ciencia:
- Inmunología Inmunología.
- Biología Molecular Biología Molecular
- Biología celular Biología celular.
Sus antecedentes:
- El factor de necrosis tumoral (TNF) está involucrado en la regresión tumoral y varias patologías como el shock séptico y la artritis reumatoide.
- El TNF existe en dos formas principales: un componente secretor de 17 kd y una forma transmembrana de 26 kd.
- Las distintas actividades biológicas de estas formas de TNF no se comprenden completamente.
Objetivo del estudio:
- Para investigar la actividad biológica de la forma transmembrana de 26 kd de TNF.
- Para comparar las funciones celulares del TNF transmembrana con el TNF secretor.
- Para determinar si el TNF requiere internalización para ejercer sus efectos citotóxicos.
Principales métodos:
- Generación de mutantes no comestibles y únicamente secrebles del TNF.
- Estudiar las actividades biológicas de estos mutantes de TNF diseñados.
- Evaluación de los efectos citotóxicos del TNF en el tumor y las células infectadas por virus.
Principales resultados:
- Un mutante no comestible del TNF transmembrana de 26 kd mata eficazmente a las células diana a través del contacto directo de célula a célula.
- El TNF no necesita ser internalizado por las células diana para inducir la muerte celular.
- La forma transmembrana del TNF media la citotoxicidad localizada.
Conclusiones:
- La forma transmembrana integral de TNF de 26 kd posee una actividad biológica distinta en comparación con el componente secretor.
- Es probable que el TNF transmembrana funcione in vivo para la matanza localizada de células tumorales y otros objetivos.
- Esta acción localizada contrasta con la bioactividad sistémica observada para la forma secretora del TNF.
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