FUCOIDAN INHIBITS LEUKOCYTE RECRUITMENT IN A MODEL PERITONEAL INFLAMMATION IN RAT AND BLOCKS INTERACTION OF P-SELECTIN WITH ITS CARBOHYDRATE LIGAND

Neutrophil recruitment into systemic inflammatory sites in vivo is tho ught to be initiated by selectin-mediated endothelial adherence. The e ffect of fucoidan (natural sulfated polymer of L-fucose) on the select in dependent PMN migration into rat peritoneum following the induction of inflammation by peptone injection was studied. Peritonitis was cha racterized by an increase in the total cell number (from 45.3 x 10(6) to 91.6 x 10(6)/rat), and by highly elevated PMN content (from 0.2% to 58%) in the rat peritoneal cavity 3 h after peptone injection. Intrav enous administration of fucoidan was found to reduce, in a dose-depend ent manner, neutrophil migration into peritoneum, Fucoidan in a dose a s low as 0.8 mg per rat caused 96.8% reduction of neutrophil extravasa tion. The inhibitory effect of fucoidan was also dependent on the time intervals between the peptone and fucoidan injections. The maximal in hibitory effect of fucoidan was observed within the first 15 min after the induction of peritonitis and it was maintained at a level of 80% during 1.5 h. Administration of fucoidan 2.5 h after peptone injection had practically no effect on PMN extravasation. Since P-selectin is k nown to play a key role at the earlier stages of PMN extravasation, it was suggested that the inhibitory effect of fucoidan was mostly due t o its interaction with P-selectin. The in vitro experiments demonstrat ed the high affinity of fucoidan for both isolated P-selectin and P-se lectin in plasma membranes of activated platelets.