CYTOTOXICITY IN L929 MURINE FIBROSARCOMA CELLS AFTER TRIGGERING OF TRANSFECTED HUMAN P75 TUMOR-NECROSIS-FACTOR (TNF) RECEPTOR IS MEDIATED BY ENDOGENOUS MURINE TNF

被引：43

作者：

VERCAMMEN, D ^{[1
]}

VANDENABEELE, P ^{[1
]}

DECLERCQ, W ^{[1
]}

VANDECRAEN, M ^{[1
]}

GROOTEN, J ^{[1
]}

FIERS, W ^{[1
]}

机构：

[1] STATE UNIV GHENT,MOLEC BIOL LAB,B-9000 GHENT,BELGIUM

来源：

CYTOKINE | 1995年 / 7卷 / 05期

关键词：

D O I：

10.1006/cyto.1995.0063

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

We compared the biological function of the human tumor necrosis factor receptors p55 (hTNF-R55) and p75 (hTNF-R75) expressed in the murine (m) fibrosarcoma cell line L929. Receptor-specific triggering of hTNF-R55 in transfected L929 cells by agonistic monoclonal antibodies or hTNF-R32WS86T, a hTNF-R55-specific mutant of hTNF, resulted in cytotoxicity. Specific clustering of hTNF-R75 in transfected L929 cells by agonistic monoclonal antibodies or hTNF-D143F, a hTNF-R75-specific mutant of hTNF also induced cytotoxicity, albeit at low level. In both cases, the cytotoxic activity of receptor clustering could be synergized by addition of 20 mM LiCl. Remarkably, cytotoxicity induced after R75 triggering in transfected L929 cells could be completely abolished by addition of neutralizing anti-mTNF antibodies, in contrast to cell killing seen after specific R55 clustering. No soluble mTNF could be demonstrated using a sensitive biological assay, although L929 cells were expressing low levels of mTNF-specific mRNA as shown by PCR. These data clearly demonstrate that minute amounts of endogenously produced TNF can be a key mediator in R75-mediated cytotoxicity. Presumably. the latter efficiently traps the ligand and transfers it to TNF-R55, and/or by binding it, protects the endogenously made TNF from inactivation. (C) 1995 Academic Press Limited.

引用

页码：463 / 470

页数：8

共 34 条

[1]

Fiers W., Tumour necrosis factor, pp. 65-119, (1993)

[2]

Beutler B., Tumor Necrosis Factors, (1992)

[3]

Vassalli P., The pathophysiology of tumor necrosis factors, Annu Rev Immunol, 10, pp. 411-452, (1992)

[4]

Bazan J.F., Emerging families of cytokines and receptors, Curr Biol, 3, pp. 603-606, (1993)

[5]

Beutler B., van Huffel C., Unraveling function in the TNF ligand and receptor families, Science, 264, pp. 667-668, (1994)

[6]

Itoh N., Yonehara S., Ishii A., Yonehara M., Mizushima S., Sameshima M., Hase A., Seto Y., Nagata S., The polypeptide encoded by the cDNA for human cell surface antigen Fas can mediate apoptosis, Cell, 66, pp. 233-243, (1991)

[7]

Tartaglia L.A., Ayres T.M., Wong G.H.W., Goeddel D.V., A novel domain within the 55 kd TNF receptor signals cell death, Cell, 74, pp. 845-853, (1993)

[8]

Itoh N., Nagata S., A novel protein domain required for apoptosis. Mutational analysis of human Fas antigen, J Biol Chem, 268, pp. 10932-10937, (1993)

[9]

Tartaglia L.A., Goeddel D.V., Two TNF receptors, Immunol Today, 13, pp. 151-153, (1992)

[10]

Slowik M.R., De Luca L.G., Fiers W., Pober J.S., Tumor necrosis factor activates human endothelial cells through the p55 tumor necrosis factor receptor but the p75 receptor contributes to activation at low tumor necrosis factor concentration, Am J Pathol, 143, pp. 1724-1730, (1993)

← 1 2 3 4 →