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首页> 美国卫生研究院文献>The Journal of Clinical Investigation >Pretranslational regulation of the synthesis of the third component of complement in human mononuclear phagocytes by the lipid A portion of lipopolysaccharide.
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Pretranslational regulation of the synthesis of the third component of complement in human mononuclear phagocytes by the lipid A portion of lipopolysaccharide.

机译：脂多糖的脂质A部分对人单核吞噬细胞中补体第三成分合成的翻译前调节。

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摘要

The third component of complement (C3) is a plasma glycoprotein with a variety of biologic functions in the initiation and maintenance of host response to infectious agents. While the hepatocyte is the primary source of plasma C3, mononuclear phagocytes contribute to the regulation of tissue availability of C3. Lipopolysaccharide (LPS), a constituent of cell walls of gram-negative bacteria, consists of a polysaccharide moiety (core polysaccharide and O antigen) covalently linked to a lipid portion (lipid A). Using metabolic labeling with [35S]methionine, immunoprecipitation, and SDS-polyacrylamide gel electrophoresis, we examined the effects of LPS on synthesis of C3 by human mononuclear phagocytes as well as synthesis of the second component of complement (C2), factor B, lysozyme, and total protein. LPS increased C3 synthesis 5-30-fold without affecting the kinetics of secretion of C3 or the synthesis of C2, lysozyme, or total protein. Factor B synthesis was consistently increased by LPS. Experiments with lipid A-inactivated LPS (alkaline treated), LPS from a polysaccharide mutant strain, and lipid X (a lipid A precursor) indicated that the lipid A portion is the structural element required for this effect. Northern blot analysis demonstrated at least a fivefold increase in C3 mRNA in LPS-treated monolayers, which suggests that the regulation of the increase in C3 synthesis is pretranslational. C2 mRNA and factor B mRNA were increased approximately twofold. The availability of specific gene products in human mononuclear phagocytes that respond to LPS should permit understanding of the molecular regulation of more complex functions of these cells elicited by LPS in which multiple gene products are coordinately expressed.
机译：补体（C3）的第三个成分是血浆糖蛋白，在引发和维持宿主对传染原的反应中具有多种生物学功能。肝细胞是血浆C3的主要来源，而单核吞噬细胞则有助于调节C3的组织利用率。脂多糖（LPS）是革兰氏阴性细菌细胞壁的组成部分，由与脂质部分（脂质A）共价连接的多糖部分（核心多糖和O抗原）组成。使用[35S]蛋氨酸的代谢标记，免疫沉淀和SDS-聚丙烯酰胺凝胶电泳，我们检查了LPS对人单核吞噬细胞合成C3以及补体第二成分（C2），因子B，溶菌酶的合成的影响和总蛋白。 LPS将C3合成增加了5-30倍，而没有影响C3分泌或C2，溶菌酶或总蛋白合成的动力学。 LPS持续增加因子B的合成。用脂质A灭活的LPS（经碱处理），来自多糖突变菌株的LPS和脂质X（脂质A前体）进行的实验表明，脂质A部分是实现此作用所需的结构元素。 Northern印迹分析表明，经LPS处理的单层细胞中C3 mRNA至少增加了五倍，这表明C3合成增加的调控是翻译前的。 C2 mRNA和因子B mRNA大约增加了两倍。在对LPS作出反应的人单核吞噬细胞中特定基因产物的可用性应允许理解由LPS引起的这些细胞的更复杂功能的分子调控，其中多个基因产物被协调表达。

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