Inhibition of complement activation by natural sulfated polysaccharides (fucans) from brown seaweed.
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.
Blondin
C
C
CNRS URA502, Université Paris Nord, Villetaneuse, France.
Fischer
E
E
Boisson-Vidal
C
C
Kazatchkine
M D
MD
Jozefonvicz
J
J
D003167:Complement Activation / Q000187:drug effects*; D003175:Complement C2 / Q000096:biosynthesis; D050679:Complement C2b; D050577:Complement C3-C5 Convertases / Q000378:metabolism; D003179:Complement C3b / Q000096:biosynthesis; D003181:Complement C4 / Q000378:metabolism; D015935:Complement C4b / Q000096:biosynthesis; D003170:Complement Pathway, Alternative / Q000187:drug effects; D003171:Complement Pathway, Classical / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D000459:Phaeophyceae / Q000737:chemistry*; D011134:Polysaccharides / Q000494:pharmacology*
D003175:Complement C2; D050679:Complement C2b; D003181:Complement C4; D011134:Polysaccharides; D003179:Complement C3b; D015935:Complement C4b; D050577:Complement C3-C5 Convertases