Active and zymogen forms of granzyme B are constitutively released from cytotoxic lymphocytes in the absence of target cell engagement.
Immunol Cell Biol
; 87(3): 249-54, 2009.
Article
en En
| MEDLINE
| ID: mdl-19079360
ABSTRACT
Granzyme B (GrB) plays a well-established intracellular role in cytotoxic lymphocyte (CL)-mediated killing of abnormal cells; however, emerging evidence suggests that it participates in extracellular matrix remodeling and target cell destruction through anoikis. As these processes require the release of GrB from the CL into the extracellular environment, we examined the secretion of GrB from natural killer (NK) cells and cytotoxic T lymphocytes (CTLs). We found that a proportion of GrB is constitutively secreted by both CTLs and NK cells in the absence of target cell engagement. In NK cells, the protease is primarily released in an active form through secretory granules. By contrast, T lymphocytes primarily secrete inactive GrB zymogen, bypassing the granules. The release of GrB through two routes from unconjugated CLs suggests that it functions outside the cell and may contribute to pathology in cases of immune dysregulation, such as familial hemophagocytic lymphohistiocytosis (FHL). Our findings also predict the existence of an extracellular activator of GrB.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Células Asesinas Naturales
/
Linfocitos T Citotóxicos
/
Precursores Enzimáticos
/
Granzimas
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Immunol Cell Biol
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2009
Tipo del documento:
Article
País de afiliación:
Australia