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Extracellular Activities of Human Granzymes
1Department of Microbiology and Immunology, University of Texas Medical Branch, 3.162 Medical Research Building, 11th and Mechanic, Galveston, Texas, 77555-1019
Cellular Immunology
|July 10, 1996
Summary
Human granzyme A, a cytotoxic cell protease, can activate immune cells like fibroblasts to produce cytokines. This suggests granzyme A has extracellular immunoregulatory functions beyond cell killing.
Area of Science:
- Immunology
- Cell Biology
- Protease Function
Background:
- Granzymes are key in cytotoxic cell-mediated apoptosis induction.
- Cytotoxic cells constitutively secrete granzymes, suggesting potential extracellular roles.
- Thrombin acts as an activation molecule, hinting at similar protease functions.
Purpose of the Study:
- To investigate if granzymes can function as extracellular activation molecules.
- To determine if granzyme A induces cytokine production in non-cytotoxic cells.
Main Methods:
- Purified human granzyme A was applied to human lung fibroblasts and other cell lines.
- Cytokine production (IL6, IL8) was measured.
- The effect of a serine protease inhibitor (3,4-dichloroisocoumarin) on cytokine induction was assessed.
Main Results:
- Purified human granzyme A induced IL6 and IL8 production in human lung fibroblasts.
- Cytokine induction was blocked by the serine protease inhibitor 3,4-dichloroisocoumarin.
- Fibroblast and epithelial cell lines responded to granzyme A by producing cytokines.
Conclusions:
- Granzyme A acts as an activation molecule, independent of its role in apoptosis.
- Granzyme A can induce cytokine production in various cell types, suggesting immunoregulatory functions.
- These findings highlight a novel extracellular role for granzymes in immune regulation.