FUCOIDIN, A POTENT INHIBITOR OF LEUKOCYTE ROLLING, PREVENTS NEUTROPHIL INFLUX INTO PHORBOL-ESTER-INDUCED INFLAMMATORY SITES IN RABBITS LUNGS

The polysaccharide fucoidin, a homopolymer of sulfated L-fucose, is kn own, by interfering with the function of L-selectin, to inhibit leukoc yte rolling, which is an early and essential step in the process of le ukocyte extravasation into inflamed sites. We tested the inhibitory ef fect of fucoidin on neutrophil accumulation in lung inflammation induc ed by phorbol myristate acetate and peritoneal inflammation induced by thioglycollate in rabbits. Pretreatment (10 mg/kg) followed by contin uous administration (10 mg/kg/h) of fucoidin dramatically reduced the number of neutrophils recruited into the lungs (determined by neutroph il counts in bronchoalveolar lavage fluid; 97.7 +/- 0.52% reduction) a nd peritoneal cavity (determined by neutrophil counts in peritoneal la vage fluid; 98.4 +/- 1.29% reduction). Fucoidin treatment also increas ed the systemic neutrophil count. These results suggest that the inhib ition of leukocyte rolling, which may be a primary function of fucoidi n, leads to a reduction of neutrophil accumulation at inflammatory sit es, which may be beneficial for attenuating neutrophil-mediated tissue injury.