Cytokine-mediated up-regulation of CD55 and CD59 protects human hepatoma cells from complement attack

被引:67
|
作者
Spiller, OB
Criado-García, O
De Córdoba, SR
Morgan, BP
机构
[1] Univ Wales Coll Med, Dept Biochem Med, Complement Biol Grp, Cardiff CF4 4XX, S Glam, Wales
[2] Fdn Jimenez Diaz, Unidad Patol Mol, E-28040 Madrid, Spain
[3] CSIC, Ctr Invest Biol, Dept Inmunol, Madrid, Spain
来源
CLINICAL AND EXPERIMENTAL IMMUNOLOGY | 2000年 / 121卷 / 02期
关键词
hepatoma; acute phase; complement regulators; cytokines;
D O I
10.1046/j.1365-2249.2000.01305.x
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Hepatic parenchymal cells respond in many different ways to acute-phase cytokines. Some responses may protect against damage by liver-derived inflammatory mediators. Previous investigations have shown that cytokines cause increased secretion by hepatoma cells of soluble complement regulatory proteins, perhaps providing protection from complement attack. More important to cell protection are the membrane complement regulators. Here we examine, using flow cytometry and Northern blotting, the effects of different cytokines, singly or in combination, on expression of membrane-bound complement regulators by a hepatoma cell line. The combination of tumour necrosis factor-alpha, IL-1 beta, and IL-6 caused increased expression of CD55 (three-fold) and CD59 (two-fold) and decreased expression of CD46 at day 3 post-exposure. Interferon-gamma reduced expression of CD59 and strongly antagonized the up-regulatory effects on CD59 mediated by the other cytokines. Complement attack on antibody-sensitized hepatoma cells following a 3-day incubation with the optimum combination of acute-phase cytokines revealed increased resistance to complement-mediated lysis and decreased C3b deposition. During the acute-phase response there is an increased hepatic synthesis of the majority of complement effector proteins. Simultaneous up-regulation of expression of CD55 and CD59 may serve to protect hepatocytes from high local concentrations of complement generated during the acute-phase response.
引用
收藏
页码:234 / 241
页数:8
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