The transmembrane form of tumor necrosis factor is the prime activating ligand of the 80 kDa tumor necrosis factor receptor

M Grell; E Douni; H Wajant; M Löhden; M Clauss; B Maxeiner; S Georgopoulos; W Lesslauer; G Kollias; K Pfizenmaier; P Scheurich

doi:10.1016/0092-8674(95)90192-2

The transmembrane form of tumor necrosis factor is the prime activating ligand of the 80 kDa tumor necrosis factor receptor

Cell. 1995 Dec 1;83(5):793-802. doi: 10.1016/0092-8674(95)90192-2.

Authors

M Grell¹, E Douni, H Wajant, M Löhden, M Clauss, B Maxeiner, S Georgopoulos, W Lesslauer, G Kollias, K Pfizenmaier, P Scheurich

Affiliation

¹ Institute of Cell Biology and Immunology, University of Stuttgart, Federal Republic of Germany.

PMID: 8521496
DOI: 10.1016/0092-8674(95)90192-2

Abstract

The 60 kDa tumor necrosis factor receptor (TNFR60) is regarded as the major signal transducer of TNF-induced cellular responses, whereas the signal capacity and role of the 80 kDa TNFR (TNFR80) remain largely undefined. We show here that the transmembrane form of TNF is superior to soluble TNF in activating TNFR80 in various systems such as T cell activation, thymocyte proliferation, and granulocyte/macrophage colony-stimulating factor production. Intriguingly, activation of TNFR80 by membrane TNF can lead to qualitatively different TNF responses such as rendering resistant tumor cells sensitive to TNF-mediated cytotoxicity. This study demonstrates that the diversity of TNF effects can be controlled through the differential sensitivity of TNFR80 for the two forms of TNF and suggests an important physiological role for TNFR80 in local inflammatory responses.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antibodies, Monoclonal
Base Sequence
CHO Cells
Cell Division
Cell Membrane
Cells, Cultured
Coculture Techniques
Cricetinae
Cytotoxicity, Immunologic / immunology
Granulocyte-Macrophage Colony-Stimulating Factor / biosynthesis
HLA-DR Antigens / biosynthesis
Humans
Kinetics
Ligands
Lymphocyte Activation / drug effects
Mice
Molecular Sequence Data
Receptors, Tumor Necrosis Factor / agonists
Receptors, Tumor Necrosis Factor / immunology*
Receptors, Tumor Necrosis Factor / metabolism
Signal Transduction / immunology*
Solubility
T-Lymphocytes / immunology
Thymus Gland / cytology
Tumor Cells, Cultured
Tumor Necrosis Factor-alpha / chemistry
Tumor Necrosis Factor-alpha / immunology*
Tumor Necrosis Factor-alpha / metabolism
Tumor Necrosis Factor-alpha / pharmacology

Substances

Antibodies, Monoclonal
HLA-DR Antigens
Ligands
Receptors, Tumor Necrosis Factor
Tumor Necrosis Factor-alpha
Granulocyte-Macrophage Colony-Stimulating Factor