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Soluble and cell surface receptors for tumor necrosis factor
D Wallach1, H Engelmann, Y Nophar
1Department of Molecular Genetics and Virology, Weizmann Institute of Science, Rehovot, Israel.
Agents and Actions. Supplements
|January 1, 1991
Summary
Tumor necrosis factor (TNF) signals through cell surface receptors, not the cytokine itself. Soluble forms of these TNF receptors, found in serum, can inhibit TNF activity and regulate cellular responses.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Tumor necrosis factor (TNF) mediates cellular functions via high-affinity cell surface receptors.
- Two distinct TNF receptor types have been identified, differentially expressed across cell types.
- The cDNAs for both TNF receptors have been successfully cloned.
Purpose of the Study:
- To investigate the signaling mechanism of TNF, focusing on the role of its receptors.
- To explore the structural similarities and differences between the two TNF receptor types.
- To understand the origin and function of soluble TNF receptors.
Main Methods:
- Analysis of TNF receptor structure and function.
- Cloning of TNF receptor cDNAs.
- Detection and quantification of soluble TNF receptors in biological fluids.
Main Results:
- Antibodies targeting the p55, type I TNF receptor can elicit TNF-like effects, indicating receptor-mediated signaling.
- Intracellular domains of the two receptors differ, suggesting distinct functional roles.
- Extracellular domains share homologous cysteine-rich repeats, similar to other growth factor receptors.
- Soluble TNF receptors, corresponding to extracellular domains, are present in urine and serum.
- Serum levels of soluble TNF receptors elevate during certain pathologies.
- Soluble TNF receptors are released via proteolytic cleavage and inhibit TNF activity.
Conclusions:
- TNF receptor activation, not TNF binding alone, initiates cellular responses.
- Soluble TNF receptors act as physiological regulators, attenuating TNF activity.
- Soluble TNF receptor levels may serve as biomarkers in pathological conditions.