Relationships between chemical characteristics and anticomplementary activity of fucans
Relationships between chemical characteristics and anticomplementary activity of fucans
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DOI：
10.1016/0142-9612(96)88710-2
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发表时间：
1996-03-01
期刊：
影响因子：
14
通讯作者：
Jozefonvicz, J
中科院分区：
文献类型：
--
作者：
Blondin, C;Chaubet, F;Jozefonvicz, J
我们以前已经表明，低分子量的岩藻聚糖提取的褐藻Ascophyllum nodosum强烈抑制体外人补体激活，其作用机制在很大程度上阐明。我们进一步研究了岩藻聚糖的分子量和化学组成对其抗补体活性的影响。岩藻聚糖的12个片段（分子量范围从4100到214 000）防止绵羊红细胞（经典途径）和兔红细胞（替代途径）补体介导的溶血的能力随着分子量的增加而增加，并分别达到40 000和13 500的平台。最有效的岩藻聚糖组分在抑制经典途径中的活性是肝素的40倍。然而，它们在抑制旁路途径方面与肝素一样活跃。此外，我们还开发了一种基于CH 50方案的溶血试验，可区分补体蛋白的激活剂和抑制剂。虽然不同岩藻聚糖片段内的甘露糖含量没有变化，但半乳糖和葡萄糖醛酸含量随着活性的增加而增加，这表明这些残基对于完全的抗互补活性应该是必不可少的。同时，硫酸基团似乎是必要的，但显然不是岩藻聚糖的抗互补活性的充分要求。总之，这些数据说明了岩藻聚糖作为潜在抗炎剂的前景。
We have shown previously that a low-molecular-weight fucan extracted from the brown seaweed Ascophyllum nodosum strongly inhibited human complement activation in vitro and its mechanism of action was largely elucidated. We further investigated the influence of molecular weight and chemical composition of fucan on its anticomplementary activity. The capacity of 12 fragments of fucan (ranging from a molecular weight of 4100 to 214 000) to prevent complement-mediated haemolysis of sheep erythrocytes (classical pathway) and of rabbit erythrocytes (alternative pathway) increased with increasing molecular weight, and reached a plateau for 40 000 and 13 500, respectively. The most potent fucan fractions were 40-fold more active than heparin in inhibiting the classical pathway. They were, however, as active as heparin in inhibiting the alternative pathway. In addition, we have developed a haemolytic test based on the CH50 protocol, which allows discrimination between activators and inhibitors of complement proteins. Although the mannose content within the different fucan fragments did not vary, the galactose and glucuronic acid contents increased with increasing activity, suggesting that these residues should be essential for full anticomplementary activity. Meanwhile, sulphate groups appeared to be necessary, but were clearly not a sufficient requirement for anticomplementary activity of fucans. Taken together, these data illustrate the prospects for the use of fucans as potential anti-inflammatory agents.