INHIBITION OF LEUKOCYTE ROLLING WITH POLYSACCHARIDE FUCOIDIN PREVENTSPLEOCYTOSIS IN EXPERIMENTAL MENINGITIS IN THE RABBIT

Inflammatory recruitment of leukocytes into the cerebrospinal fluid (C SF) during bacterial meningitis has been shown to contribute significa ntly to the neurological damage commonly associated with this serious disease. In this study we tested whether or not inhibition of leukocyt e rolling, a precondition for firm leukocyte adhesion to vascular endo thelium in vivo, may reduce CSF leukocyte recruitment and associated i nflammatory changes in rabbits with experimental meningitis. As docume nted 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 h omopolymer of sulfated L-fucose known to block the function of the leu kocytic ''rolling receptor'' L-selectin. Moreover, fucoidin treatment dramatically reduced the accumulation of both leukocytes and plasma pr otein in the CSF of rabbits challenged intrathecally with pneumococcal antigen. These main findings thus illustrate that inhibition of leuko cyte 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 meningi tis.