Däubener W, Nockemann S, Gutsche M, Hadding U
Institut für Medizinische, Mikrobiologie und Virologie, Heinrich-Heine-Universität, Düsseldorf, Germany.
Eur J Immunol. 1995 Mar;25(3):688-92. doi: 10.1002/eji.1830250309.
Interferon-gamma (IFN-gamma) is a potent immune regulatory cytokine and is, in addition, involved in the induction of antiparasitic effector mechanisms in different cell types. The first step of IFN-gamma action is its binding to a specific receptor. Furthermore, it has been shown that IFN-gamma binds with a great affinity to the heparin-like structure of heparan sulfate, which is localized in basement membranes and on cell surfaces. In this study, we analyze the effect of heparin and heparan sulfate on three different IFN-gamma-mediated activities inducible in human glioblastoma cells (87HG31 and 86HG39). We find firstly that heparin is able to inhibit IFN-gamma-mediated induction of major histocompatibility complex (MHC) class II antigen expression on 87HG31 cells, an effect which can be abrogated by protamine. Secondly, we show that heparin inhibits the IFN-gamma-induced toxoplasmostasis within 86HG39 cells in a dose-dependent fashion, and thirdly that heparin inhibits the IFN-gamma-mediated induction of the tryptophan-degrading enzyme indoleamine 2,3-dioxygenase. In contrast to IFN-gamma-induced effects, the activity of other cytokines, such as interleukin (IL)-1, IL-2 and IL-6, is not influenced by heparin. The possible mechanism of heparin-induced inhibition of IFN-gamma is discussed.
干扰素-γ（IFN-γ）是一种强效的免疫调节细胞因子，此外，它还参与诱导不同细胞类型中的抗寄生虫效应机制。IFN-γ作用的第一步是与特定受体结合。此外，研究表明IFN-γ与硫酸乙酰肝素的类肝素结构具有高亲和力，硫酸乙酰肝素定位于基底膜和细胞表面。在本研究中，我们分析了肝素和硫酸乙酰肝素对人胶质母细胞瘤细胞（87HG31和86HG39）中三种不同的IFN-γ介导的可诱导活性的影响。我们首先发现肝素能够抑制IFN-γ介导的87HG31细胞上主要组织相容性复合体（MHC）II类抗原表达的诱导，鱼精蛋白可消除这种作用。其次，我们表明肝素以剂量依赖的方式抑制86HG39细胞内IFN-γ诱导的弓形虫生长停滞，第三，肝素抑制IFN-γ介导的色氨酸降解酶吲哚胺2,3-双加氧酶的诱导。与IFN-γ诱导的效应相反，其他细胞因子如白细胞介素（IL）-1、IL-2和IL-6的活性不受肝素影响。本文讨论了肝素诱导抑制IFN-γ的可能机制。
