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Selective degradation of tumor necrosis factor in sensitive cells, and production of membrane-active substance
Abstract:
The mode of action of tumor necrosis factor (TNF) was studied. On treatment of TNF-sensitive L929 cells with radioiodinated TNF, the TNF molecule was found to be internalized into the cells and extensively degraded. On treatment of TNF-insensitive embryonic fibroblast cells with TNF, less TNF was internalized and it was not degraded appreciably. The L929 cells excreted the degradation products of TNF into the culture medium, and this medium showed activity for degradation of liposomes composed of phosphatidylserine and phosphatidylcholine. The sensitive cells may contain some specific proteinase that cleaves TNF molecules.
Insights
Tumor necrosis factor (TNF) is degraded by sensitive cells, which release products that break down liposomes. Insensitive cells internalize and degrade less TNF, suggesting a specific proteinase in sensitive cells.
Area of Science:
- Cell Biology
- Immunology
- Biochemistry
Background:
- Tumor necrosis factor (TNF) is a key cytokine involved in inflammation and immunity.
- Understanding the cellular mechanisms of TNF action is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the cellular uptake, degradation, and action of tumor necrosis factor (TNF).
- To identify potential differences in TNF processing between sensitive and insensitive cell lines.
Main Methods:
- Treatment of L929 (TNF-sensitive) and embryonic fibroblast (TNF-insensitive) cells with radioiodinated TNF.
- Analysis of TNF internalization and degradation within cells.
- Assessment of degradation products in the culture medium.
- Liposome degradation assays.
Main Results:
- TNF-sensitive L929 cells internalized and extensively degraded TNF, excreting products into the medium.
- TNF-insensitive cells showed less internalization and minimal degradation of TNF.
- The medium from L929 cells degraded liposomes composed of phosphatidylserine and phosphatidylcholine.
- These findings suggest the presence of a specific proteinase in sensitive cells responsible for TNF cleavage.
Conclusions:
- Cellular processing of TNF differs significantly between sensitive and insensitive cell lines.
- Degradation products of TNF released by sensitive cells possess lipolytic activity.
- A specific proteinase likely mediates TNF degradation in sensitive cells, contributing to their response.