Journal
IMMUNITY
Volume 29, Issue 5, Pages 720-733Publisher
CELL PRESS
DOI: 10.1016/j.immuni.2008.08.014
Keywords
-
Categories
Funding
- Alexander von Humboldt Foundation
- Fundacion Agencia Aragonesa para Investigacion y Desarrollo
- [5ROlAI04494-03]
- [KO1 CA100095]
Ask authors/readers for more resources
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 (interfeukin-1 beta [IL-1 beta], TNF alpha, and IL-6) that were blocked by a caspase-1 inhibitor. Moreover, murine GzmA and GzmA(+) cytotoxic T lymphocytes (CTLs) induce IL-1 beta 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available