Outside-to-inside signal through the membrane TNF-alpha induces E-selectin (CD62E) expression on activated human CD4+ T cells

• Published in: The Journal of immunology (1950) Vol. 166; no. 1; pp. 130 - 136
• Main Authors: Harashima, S, Horiuchi, T, Hatta, N, Morita, C, Higuchi, M, Sawabe, T, Tsukamoto, H, Tahira, T, Hayashi, K, Fujita, S, Niho, Y
• Format: Journal Article
• Language: English
• Published: United States 01.01.2001
• Subjects: CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD40 Ligand - physiology; Cell Communication - immunology; Coculture Techniques; E-Selectin - biosynthesis; Fas Ligand Protein; fas Receptor - physiology; HeLa Cells; Humans; Intracellular Fluid - immunology; Intracellular Fluid - physiology; Jurkat Cells; Ligands; Lymphocyte Activation; Membrane Glycoproteins - genetics; Membrane Glycoproteins - physiology; Signal Transduction - immunology; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; T-Lymphocyte Subsets - virology; Transfection; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - physiology; Up-Regulation - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.166.1.130

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.