Acute phase mediated change in glycosylation of rat alpha 1-acid glycoprotein in transgenic mice.
Acute phase mediated change in glycosylation of rat alpha 1-acid glycoprotein in transgenic mice.
复制标题
急性期介导转基因小鼠中大鼠α1-酸性糖蛋白糖基化的变化。
DOI：
10.1093/glycob/1.3.265
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发表时间：
1991
期刊：
影响因子：
4.3
通讯作者：
Baumann,H
中科院分区：
文献类型：
--
作者：
Mackiewicz,A;Dewey,MJ;Berger,FG;Baumann,H
携带大鼠α1-酸性糖蛋白基因的转基因小鼠在血浆中表达该蛋白的浓度等于或超过急性期大鼠的浓度。由于基础水平较高，这些转基因小鼠代表了一种独特的实验系统，用于确定AGP基本上未知的功能。由于AGP的碳水化合物部分在急性期发生了变化，寡糖结构对AGP的免疫调节活性具有重要作用，因此用凝集素亲和免疫电泳法对转基因小鼠中的大鼠AGP进行了鉴定。与大鼠不同，转基因小鼠血浆中的AGP主要由强烈的刀豆蛋白A反应形式组成。急性期AGP血浆总浓度增加数倍，并向中度刀豆蛋白A反应形式转变。内源性急性时相血浆蛋白结合珠蛋白的刀豆蛋白A反应形式也有类似的变化。为了明确炎症因子在AGP产生中的作用，制备了肝细胞的原代培养。与体内相比，从组织培养上清液中回收的AGP主要代表刀豆蛋白A-非反应形式。重组人白介素1、白介素6和地塞米松刺激细胞产生刀豆蛋白A反应性AGP。结果表明，AGP的糖基化模式受急性期的调节，但在组织培养中形成的AGP与肝细胞分泌的糖基化模式并不一致。这一发现需要评估AGP的哪种可能的糖基化形式在体内具有显著的功能意义。
Transgenic mouse lines carrying the gene for rat α1-acid glycoprotein (AGP) express the protein in the plasma at concentrations equal to or exceeding that of acute phase rats. Owing to the high basal level, these transgenic mice represent a unique experimental system for defining the largely unknown function of AGP. Since the carbohydrate moiety of AGP has been found to be changed during acute phase and the oligosaccharide structure to be important for immunomodulating activity of the protein, the rat AGP in transgenic mice was characterized by lectin-affinity immuno-electrophoresis. Unlike in the rat, the AGP in the transgenic mouse plasma consisted primarily of strongly concanavalin A-reactive forms. Acute phase mediated a several-fold increase in the total plasma concentration of AGP concomitant with a shift toward moderately concanavalin A-reactive forms. A similar change in concanavalin A-reactive forms was observed for the endogenous acute phase plasma protein haptoglobin. To define the role of inflammatory factors in AGP production, primary cultures of hepatocytes were prepared. In contrast toin vivo, the AGP recovered from tissue culture medium represented primarily the concanavalin A-non-reactive form. Treatment of the cells with recombinant human interleukin-1, interleukin-6 and dexamethasone stimulated the production of concanavalin A-reactive AGP forms. The data indicate that the glycosylation pattern of plasma-resident AGP is modulated by acute phase, but that the profile of AGP forms does not coincide with that secreted by hepatocytes in tissue culture. This finding demands an assessment of which of the possible glycosylated forms of AGP is functionally significantin vivo.