Inhibition of leukocyte rolling with polysaccharide fucoidin prevents pleocytosis in experimental meningitis in the rabbit.

Abstract

Inflammatory recruitment of leukocytes into the cerebrospinal fluid (CSF) during bacterial meningitis has been shown to contribute significantly to the neurological damage commonly associated with this serious disease. In this study we tested whether or not inhibition of leukocyte rolling, a precondition for firm leukocyte adhesion to vascular endothelium in vivo, may reduce CSF leukocyte recruitment and associated inflammatory changes in rabbits with experimental meningitis. As documented by intravital microscopy of small venules in the rabbit mesentery and tenuissimus muscle, leukocyte rolling was rapidly and profoundly reduced by intravenous treatment with the polysaccharide fucoidin, a homopolymer of sulfated L-fucose known to block the function of the leukocytic "rolling receptor" L-selectin. Moreover, fucoidin treatment dramatically reduced the accumulation of both leukocytes and plasma protein in the CSF of rabbits challenged intrathecally with pneumococcal antigen. These main findings thus illustrate that inhibition of leukocyte rolling, an early and obligatory step in the process of leukocyte extravasation, may be an effective therapeutic approach to attenuate leukocyte-dependent central nervous system damage in bacterial meningitis. (J. Clin. Invest. 1994. 93:929-936.)

Visualization and in situ analysis of leukocyte trafficking into the ankle joint in a systemic murine model of rheumatoid arthritis

“…The strong reduction in the number of adherent cells in the presence of a modest (20-30%) inhibition of rolling interactions in the synovial venules of fucoidin-treated mice was somewhat in conflict with previous in vivo findings that fucoidin strongly inhibited cell rolling, but not firm adhesion (23)(24)(25). The discrepancy prompted us to examine whether the selectin antagonist reduced firm adhesion by disrupting existing adhesion interactions (thus resulting in an enhanced detachment rate) or by preventing the arrest and subsequent firm adhesion of rolling cells.…”

Fucoidan Enhances the Survival and Sustains the Number of Splenic Dendritic Cells in Mouse Endotoxemia

“…The effects of fucoidan on survival rate and spleen function were prophylactic, rather than therapeutic, suggesting that fucoidan requires time to protect target cells against the harmful effects of LPS. Based on previous studies, fucoidan blocks selectin-dependent leukocyte adhesion/rolling [13,14] and inhibit microvascular thrombus formation [15]. It is thus suggested that fucoidan may affect blood circulation dysfunction by LPS in mice.…”

A Novel Biological Activity for Galectin-1

“…For instance, inhibition of selectin binding to sialyl Lewis X by the polysaccharide fucoidin, results in reduction of PMN rolling and extravasation. 40,41 These sugars may be expressed on several membrane proteins, 42 including those mediating L-selectin and P-selectin binding to their counterligands. 37 It is of interest that a recent study has reported a role for complex sugars in mediating the anti-inflammatory effects of heparin derivatives.…”