Activity of Monosaccharide Lipid A Analogues in Human Monocytic Cells as Agonists or Antagonists of Bacterial Lipopolysaccharide
Activity of Monosaccharide Lipid A Analogues in Human Monocytic Cells as Agonists or Antagonists of Bacterial Lipopolysaccharide
复制标题
人单核细胞中单糖脂质 A 类似物作为细菌脂多糖激动剂或拮抗剂的活性
作者：
M. Matsuura;M. Kiso;A. Hasegawa
细菌脂多糖（LPS）的脂质A部分在内毒素介质的产生中起着重要作用。已经表明人和鼠巨噬细胞对脂质A样结构的不同反应。我们研究了一系列结构相关的单糖脂质A类似物激活人巨噬细胞U937细胞和外周血单个核细胞产生肿瘤坏死因子-α和白细胞介素-6的效力，并与其激活小鼠巨噬细胞RAW 264.7细胞的效力进行了比较。发现其中两种类似物具有足够的效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-葡糖胺、磷酰基和具有确定碳链长度（C14和C12）的酰基。分子组分的比例与脂质A的完整二糖结构成比例（2：2：6）。具有两个或四个C14酰基和具有三个酰基但包括C10或C16酰基的对鼠细胞有活性的其他类似物未显示出LPS激动活性，但对人细胞显示出LPS拮抗活性。小鼠细胞中的LPS拮抗类似物在人细胞中也显示出拮抗活性。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，其比被鼠巨噬细胞识别所需的结构特征更严格，并且宽的脂质A样结构被人细胞识别为LPS拮抗剂，但被鼠细胞识别为LPS激动剂或拮抗剂。
ABSTRACT 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.
影响因子：
56.9
作者：
WRIGHT, SD;RAMOS, RA;MATHISON, JC
通讯作者：
MATHISON, JC
影响因子：
56.9
作者：
DING, AH;PORTEU, F;NATHAN, CF
通讯作者：
NATHAN, CF
DOI：
10.1016/s0021-9258(18)55023-7
发表时间：
1991-10
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Douglas T. GolenbockSQll;Randolph;HamptonIIQ;N. Qureshi;K. Takayama;Christian R. H. RaetzQ
通讯作者：
Douglas T. GolenbockSQll;Randolph;HamptonIIQ;N. Qureshi;K. Takayama;Christian R. H. RaetzQ