RELATIONSHIPS BETWEEN CHEMICAL CHARACTERISTICS AND ANTICOMPLEMENTARY ACTIVITY OF FUCANS

We have shown previously that a low-molecular-weight fucan extracted f rom the brown seaweed Ascophyllum nodosum strongly inhibited human com plement activation in vitro and its mechanism of action was largely el ucidated. We further investigated the influence of molecular weight an d 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 e rythrocytes (classical pathway) and of rabbit erythrocytes (alternativ e pathway) increased with increasing molecular weight, and reached a p lateau for 40 000 and 13 500, respectively. The most potent fucan frac tions were 40-fold more active than heparin in inhibiting the classica l 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 activa tors and inhibitors of complement proteins. Although the mannose conte nt within the different fucan fragments did not vary, the galactose an d glucuronic acid contents increased with increasing activity, suggest ing that these residues should be essential for full anticomplementary activity. Meanwhile, sulphate groups appeared to be necessary, but we re clearly not a sufficient requirement for anticomplementary activity of fucans. Taken together, these data illustrate the prospects for th e use of fucans as potential anti-inflammatory agents.