[Sulfated polysaccharides as inhibitors of receptor activity of P-selectin and P-selectin-dependent inflammation]

The inhibitory effects of sulfated polysaccharides-fucoidan and heparin on P-selectin-ligand interaction in vitro and on the ability of fucoidan to inhibit the leukocyte extravasation in rat peritonitis were studied. The lectin activity of P-selectin in vitro was based on its ability to bind lectin-labeled synthetic ligand, Sialyl-Lea/x, conjugated with polyacrylamide (PAA). Fucoidan and heparin inhibited binding of labeled ligand to both purified P-selectin and the activated platelets expressing P-selectin on their surface. The inhibitory effect of fucoidan 100-fold higher than that of heparin. As P-selectin plays an important role at an earlier stage of the inflammation process, the antiinflammatory action of fucoidan on P-selectin-dependent peritonitis in rats was studied. Peritonitis was induced by intraperitoneal injection of the peptone solution and was characterized by an increase in total cell number and neutrophil percentage in rat peritone exudate. Intravenous injection of fucoidan was found to cause a dose- and time-dependent reduction of neutrophil extravasation into inflamed peritoneum. The minimal dose of fucoidan, that was able to produce 96.8 +/- 2.9% inhibition of neutrophil extravasation--if administered within the first 15 min after peptone-B was 0.8 mg per rat. Significant effect of fucoidan injection (about 80% inhibition) was also obtained 1.5 h after the induction of inflammation. Fucoidan administered 2.5 h after peptone had virtually no effect on neutrophil extravasation. The data obtained show that fucoidan blocks the inflammation process at its earlier stages--most probably at the expense of its interaction with P-selectin.