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

The 60 kDa tumor necrosis factor receptor (TNFR 60) is regarded as the major signal transducer of TNF-induced cellular responses, whereas the signal capacity and role of the 80 kDa TNFR (TNFR 80) remain largely undefined. We show here that the transmembrane form of TNF is superior to soluble TNF in...

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Bibliographic Details
Published in:	Cell Vol. 83; no. 5; pp. 793 - 802
Main Authors:	Grell, Matthias, Douni, Eleni, Wajant, Harald, Löhden, Matthias, Clauss, Matthias, Maxeiner, Beate, Georgopoulos, Spiros, Lesslauer, Werner, Kollias, George, Pfizenmaier, Klaus, Scheurich, Peter
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 01-12-1995
Subjects:	Animals Antibodies, Monoclonal Base Sequence Cell Division Cell Membrane Cells, Cultured CHO Cells 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
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Summary:	The 60 kDa tumor necrosis factor receptor (TNFR 60) is regarded as the major signal transducer of TNF-induced cellular responses, whereas the signal capacity and role of the 80 kDa TNFR (TNFR 80) remain largely undefined. We show here that the transmembrane form of TNF is superior to soluble TNF in activating TNFR 80 in various systems such as T cell activation, thymocyte proliferation, and granulocyte/macrophage colony-stimulating factor production. Intriguingly, activation of TNFR 80 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 TNFR 80 for the two forms of TNF and suggests an important physiological role for TNFR 80 in local inflammatory responses.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2
ISSN:	0092-8674 1097-4172
DOI:	10.1016/0092-8674(95)90192-2