Outside-to-inside signal through the membrane TNF-alpha induces E-selectin (CD62E) expression on activated human CD4+ T cells.
The membrane TNF-alpha is known to serve as a precursor of the soluble form of TNF-alpha. Although it has been reported the biological functions of the membrane TNF-alpha as a ligand, the outside-to-inside (reverse) signal transmitted through membrane TNF-alpha is poorly understood. Here we report a novel function mediated by outside-to-inside signal via membrane TNF-alpha into the cells expressing membrane TNF-alpha. Activation by anti-TNF-alpha Ab against membrane TNF-alpha on human T cell leukemia virus (HTLV) I-infected T cell line, MT-2, or PHA-activated normal human CD4(+) T cells resulted in the induction of an adhesion molecule, E-selectin (CD62E), on the cells with the peak of 12-24 h, which completely disappeared by 48 h. When wild-type or mutant membrane TNF-alpha (R78T/S79T) resistant to proteolytic cleavage was introduced into Jurkat or HeLa cells, E-selectin was induced by the treatment with anti-TNF-alpha Ab with the similar kinetics. Membrane TNF-alpha-expressing Jurkat cells also up-regulated E-selectin when brought into cell-to-cell contact with TNF receptor-expressing HeLa cells. Northern blot analysis and RT-PCR analysis showed that the membrane TNF-alpha-mediated E-selectin expression was up-regulated at the level of transcription. These results not only confirmed our previous findings of reverse signaling through membrane TNF-alpha, but also presented evidence that E-selectin was inducible in cell types different from endothelial cells. It is strongly suggested that membrane TNF-alpha is a novel proinflammatory cell surface molecule that transmits bipolar signals in local inflammation.
Harashima
S
S
First Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Horiuchi
T
T
Hatta
N
N
Morita
C
C
Higuchi
M
M
Sawabe
T
T
Tsukamoto
H
H
Tahira
T
T
Hayashi
K
K
Fujita
S
S
Niho
Y
Y
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D023201:CD40 Ligand / Q000502:physiology; D002450:Cell Communication / Q000276:immunology; D018920:Coculture Techniques; D019040:E-Selectin / Q000096:biosynthesis*; D053222:Fas Ligand Protein; D006367:HeLa Cells; D006801:Humans; D007424:Intracellular Fluid / Q000276:immunology / Q000502:physiology; D019169:Jurkat Cells; D008024:Ligands; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000821:virology; D014162:Transfection; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000502:physiology*; D015854:Up-Regulation / Q000276:immunology; D019014:fas Receptor / Q000502:physiology
D019040:E-Selectin; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008024:Ligands; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D023201:CD40 Ligand