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A Colorimetric Assay that Specifically Measures Granzyme B Proteolytic Activity: Hydrolysis of Boc-Ala-Ala-Asp-S-Bzl
Published on: November 28, 2014
Human and mouse granzyme A induce a proinflammatory cytokine response
Sunil S Metkar1, Cheikh Menaa, Julian Pardo
1Department of Medicine, NorthShore University HealthSystem Research Institute, Evanston, IL 60201, USA.
Immunity
|October 28, 2008
Summary
Granzyme A (GzmA) causes rapid cell death via membrane damage, even without its catalytic activity. GzmA also triggers inflammatory cytokine release, highlighting its unexpected role in inflammation.
Area of Science:
- Immunology
- Cell Biology
Background:
- Granzyme A (GzmA) is primarily known as a proapoptotic protease.
- Its role in cell death and inflammation is not fully understood.
Purpose of the Study:
- To investigate the mechanisms of GzmA-induced cell death.
- To explore the non-catalytic functions of Granzymes in inflammation.
Main Methods:
- Studied GzmA-induced cell death in synergy with perforin (PFN).
- Assessed GzmA's effect on cytokine secretion in monocytic cells.
- Utilized GzmA knockout mice and GzmA-expressing cytotoxic T lymphocytes (CTLs).
Main Results:
- GzmA induces rapid necrotic cell death through membrane damage, requiring synergy with sublytic PFN.
- Both GzmA and Granzyme B (GzmB) mediate necrosis independently of catalytic activity.
- GzmA stimulates monocytic cells to secrete IL-1beta, TNFalpha, and IL-6, blocked by caspase-1 inhibition.
- Murine GzmA and CTLs induce IL-1beta in macrophages; GzmA knockout mice show resistance to LPS toxicity.
Conclusions:
- Granzyme A has a dual role in inducing rapid cell death and promoting inflammation.
- The granule secretory pathway is unexpectedly involved in inflammatory processes.
- GzmA acts as an endogenous modulator of inflammation, independent of its protease function.
