Human and mouse granzyme A induce a proinflammatory cytokine response.
Immunity
; 29(5): 720-33, 2008 Nov 14.
Article
em En
| MEDLINE
| ID: mdl-18951048
ABSTRACT
Granzyme A (GzmA) is considered a major proapoptotic protease. We have discovered that GzmA-induced cell death involves rapid membrane damage that depends on the synergy between micromolar concentrations of GzmA and sublytic perforin (PFN). Ironically, GzmA and GzmB, independent of their catalytic activity, both mediated this swift necrosis. Even without PFN, lower concentrations of human GzmA stimulated monocytic cells to secrete proinflammatory cytokines (interleukin-1beta [IL-1beta], TNFalpha, and IL-6) that were blocked by a caspase-1 inhibitor. Moreover, murine GzmA and GzmA(+) cytotoxic T lymphocytes (CTLs) induce IL-1beta from primary mouse macrophages, and GzmA(-/-) mice resist lipopolysaccharide-induced toxicity. Thus, the granule secretory pathway plays an unexpected role in inflammation, with GzmA acting as an endogenous modulator.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Leucócitos Mononucleares
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Linfócitos T Citotóxicos
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Interleucina-6
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Fator de Necrose Tumoral alfa
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Granzimas
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Interleucina-1beta
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Perforina
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article