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Published on: April 9, 2013
Red cell regulation of tumor necrosis factor-induced human neutrophil cytostatic activity
1Division of Surgical Oncology, UCLA School of Medicine 90024-1782.
Abstract:
Tumor necrosis factor (TNF) activates polymorphonuclear neutrophils (PMN) to suppress tumor cell proliferation. This cytostatic activity could be blocked by the addition of red blood cells (RBC) into the assay. TNF-induced PMN cytostatic activity was mediated by hydrogen peroxide (H2O2). RBC have two major pathways to detoxify H2O2, one by catalase and the other by the glutathione redox cycle. Therefore, the catalase inhibitor 3-amino-1,2,4-triazole (AT) and the glutathione inhibitor N-ethylmaleimide (NE) were used to assess the role of each anti-oxidant in protecting the tumor target cells. RBC, depleted of catalase by AT, no longer protected Raji tumor cells from PMN cytostatic activity. However, depletion of reduced glutathione by NE had no effect on RBC protection of tumor target cells. Thus, RBC can protect tumor cells from cytostatic activity mediated by TNF-activated PMN, and the protection is a function of catalase, but not glutathione.
Insights
Red blood cells (RBC) protect tumor cells from tumor necrosis factor (TNF)-activated neutrophil suppression. This protection relies on RBC
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Tumor necrosis factor (TNF) activates polymorphonuclear neutrophils (PMN) to inhibit tumor cell growth.
- Red blood cells (RBC) can block this TNF-induced cytostatic activity.
- Hydrogen peroxide (H2O2) mediates TNF-induced PMN cytostatic activity.
Purpose of the Study:
- To investigate the role of RBC in protecting tumor cells from TNF-activated PMN-mediated cytostasis.
- To determine whether RBC's catalase or glutathione redox cycle is responsible for this protective effect.
Main Methods:
- Utilized 3-amino-1,2,4-triazole (AT), a catalase inhibitor, and N-ethylmaleimide (NE), a glutathione inhibitor.
- Assessed the impact of RBC treated with AT or NE on the cytostatic activity of TNF-activated PMN against Raji tumor cells.
Main Results:
- RBC depleted of catalase activity by AT failed to protect Raji tumor cells from PMN-induced cytostasis.
- RBC with inhibited glutathione redox cycle (using NE) still protected tumor cells.
- These findings indicate that RBC's catalase, not its glutathione system, is crucial for protection.
Conclusions:
- Red blood cells protect tumor cells from TNF-activated PMN-mediated cytostatic effects.
- This RBC-mediated protection is dependent on the catalase enzyme, not the glutathione redox cycle.
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