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首页> 外文期刊>Infection and immunity >Activity of Monosaccharide Lipid A Analogues in Human Monocytic Cells as Agonists or Antagonists of Bacterial Lipopolysaccharide
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Activity of Monosaccharide Lipid A Analogues in Human Monocytic Cells as Agonists or Antagonists of Bacterial Lipopolysaccharide

机译：人单核细胞中单糖脂质A类似物作为细菌脂多糖的激动剂或拮抗剂的活性

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The lipid A portion of bacterial lipopolysaccharide (LPS) plays a central role in the production of endotoxic mediators. Different responses between human and murine macrophages to lipid A-like structures have been indicated. We investigated a series of structurally related monosaccharide lipid A analogues for their potency to activate human macrophage U937 cells and peripheral blood mononuclear cells for production of tumor necrosis factor-α and interleukin-6 compared with their potency to activate murine macrophage RAW264.7 cells. Two of the analogues were found to have sufficient potency to activate the human cells as well as the murine cells. These analogues comprise d-glucosamine, phosphoryl groups, and acyl groups of defined carbon chain lengths (C14 and C12) in a ratio of 1:1:3. This ratio of molecular constituents is proportional to that of the complete disaccharide structure of lipid A (2:2:6). Other analogues with two or four C14 acyl groups and with three acyl groups but including a C10 or a C16 acyl group, which are active to murine cells, showed no LPS-agonistic activity, but did show LPS-antagonistic activity, to human cells. An LPS-antagonistic analogue in the murine cells also showed antagonistic activity in human cells. These results reveal that lipid A analogues recognized as being LPS agonists by human macrophages have common structural features in monosaccharide and disaccharide structures which are more strict than those required for recognition by murine macrophages and that broad lipid A-like structures are recognized as being LPS antagonists by human cells but are recognized by murine cells as being either LPS agonists or antagonists.
机译：细菌脂多糖（LPS）的脂质A部分在内毒素介质的产生中起着核心作用。已经表明人和鼠巨噬细胞对脂质A样结构的不同反应。我们研究了一系列与结构相关的单糖脂质A类似物，它们具有激活人巨噬细胞U937细胞和外周血单核细胞产生肿瘤坏死因子-α和白介素6的能力，以及它们具有激活鼠巨噬细胞RAW264.7细胞的能力。发现其中两个类似物具有足够的能力来激活人细胞以及鼠细胞。这些类似物包含比例为1：1：3的d-氨基葡萄糖，磷酸基和定义的碳链长度（C 14 和C 12 ）的酰基。该分子组成的比例与脂质A的完整二糖结构的比例成比例（2：2：6）。具有两个或四个C 14 酰基和三个酰基但包括C 10 或C 16 酰基的其他类似物是对鼠细胞有活性，对人细胞无LPS拮抗活性，但对LPS有拮抗活性。鼠细胞中的LPS拮抗物类似物在人细胞中也表现出拮抗活性。这些结果表明，被人巨噬细胞识别为LPS激动剂的脂质A类似物在单糖和二糖结构中具有共同的结构特征，其比鼠巨噬细胞识别所必需的结构特征更严格，并且广泛的类脂A样结构被认为是LPS拮抗剂。被人细胞识别，但被鼠细胞识别为LPS激动剂或拮抗剂。

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