Blondin C, Fischer E, Boisson-Vidal C, Kazatchkine M D, Jozefonvicz J
CNRS URA502, Université Paris Nord, Villetaneuse, France.
Mol Immunol. 1994 Mar;31(4):247-53. doi: 10.1016/0161-5890(94)90121-x.
In the present study, we demonstrate that natural sulfated polysaccharides (fucans) isolated from brown seaweed are potent inhibitors of human complement activation. A fucan fraction of chromatographic molecular weight 22,600, termed BS8, was found to inhibit classical and alternative pathway activation in whole serum in a dose-dependent fashion. Fucan BS8 inhibited formation of the classical pathway C3 convertase by interfering with C1 activation or by inhibiting C4 cleavage and the interaction between C4b and C2. The fucan also inhibited formation/function of the alternative pathway C3 convertase by suppressing the binding of B to C3b and by interfering with the stabilizing function of Properdin. The inhibitory effect of fucans on formation of the C3 convertases was dependent on the molecular weight of the polysaccharide for compounds of chromatographic molecular weight below 16,600. Fucan had no effect on the function of the terminal complex. Since fucans were more efficient than heparin in inhibiting activation of the classical pathway in whole serum and exhibited a lesser specific anticoagulant activity on a molar basis, our results suggest that these natural sulfated polysaccharides have a potential for use as anti-complementary and anti-inflammatory agents.
在本研究中，我们证明从褐藻中分离出的天然硫酸化多糖（岩藻聚糖）是人类补体激活的有效抑制剂。一种色谱分子量为22,600的岩藻聚糖级分，称为BS8，被发现以剂量依赖的方式抑制全血清中的经典途径和替代途径激活。岩藻聚糖BS8通过干扰C1激活或通过抑制C4裂解以及C4b与C2之间的相互作用来抑制经典途径C3转化酶的形成。该岩藻聚糖还通过抑制B与C3b的结合以及干扰备解素的稳定功能来抑制替代途径C3转化酶的形成/功能。对于色谱分子量低于16,600的化合物，岩藻聚糖对C3转化酶形成的抑制作用取决于多糖的分子量。岩藻聚糖对末端复合物的功能没有影响。由于岩藻聚糖在抑制全血清中经典途径的激活方面比肝素更有效，并且在摩尔基础上表现出较低的特异性抗凝活性，我们的结果表明这些天然硫酸化多糖有潜力用作抗补体和抗炎剂。
