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Updated: Oct 15, 2026

A High Yield and Cost-efficient Expression System of Human Granzymes in Mammalian Cells
Published on: June 10, 2015
Soluble granzymes are released during human endotoxemia and in patients with severe infection due to gram-negative
F N Lauw1, A J Simpson, C E Hack
1Laboratory of Experimental Internal Medicine, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands. fnlauw@hotmail.com
Abstract:
Extracellular release of granzymes is considered to reflect the involvement of cytotoxic T lymphocytes and NK cells in various disease states. To obtain insight into granzyme release during bacterial infection, granzyme levels were measured during experimental human endotoxemia and in patients with melioidosis, a severe infection due to gram-negative bacteria. Plasma concentrations of granzyme A (GrA) and GrB increased transiently after endotoxin administration, peaking after 2-6 h. In patients with bacteremic melioidosis, GrA and GrB levels were elevated on admission and remained high during the 72-h study period. In whole blood stimulated with heat-killed Burkholderia pseudomallei, neutralization of tumor necrosis factor, interleukin-12, or interleukin-18 inhibited granzyme secretion, which was independent of interferon-gamma. Stimulation with endotoxin and other gram-negative and gram-positive bacteria also strongly induced the secretion of granzymes, suggesting that granzyme release is a general immune response during bacterial infection. The interaction between the cytokine network and granzymes may play an important immunoregulatory role during bacterial infections.
Insights
Granzyme A (GrA) and Granzyme B (GrB) levels increase during bacterial infections, indicating immune cell involvement. Cytokine neutralization affects granzyme release, suggesting a role in bacterial immune responses.
Area of Science:
- Immunology
- Microbiology
- Infectious Diseases
Background:
- Extracellular granzyme release signifies cytotoxic T lymphocyte and NK cell activity in disease.
- Understanding granzyme dynamics during bacterial infections is crucial for immune response insights.
Purpose of the Study:
- To investigate granzyme release patterns during bacterial infections.
- To explore the role of cytokines in granzyme secretion during bacterial challenges.
Main Methods:
- Measured plasma granzyme A (GrA) and GrB levels in experimental human endotoxemia and melioidosis patients.
- Stimulated whole blood with bacteria and assessed granzyme secretion following cytokine neutralization.
Main Results:
- Transient GrA and GrB increases observed post-endotoxin, peaking at 2-6 hours.
- Elevated GrA and GrB levels persisted in patients with bacteremic melioidosis.
- Cytokine neutralization (TNF, IL-12, IL-18) inhibited granzyme secretion, independent of interferon-gamma.
- Bacterial stimulation induced significant granzyme secretion, indicating a general immune response.
Conclusions:
- Granzyme release is a general immune response to bacterial infections.
- Cytokine networks interact with granzymes, potentially playing an immunoregulatory role.
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