Evidence that mannose recognition by splenic sinusoidal cells plays a role in the splenic entry of lymphocytes.

Previous studies demonstrated that mannan is a potent inhibitor of splenic entry of lymphocytes and mediates its inhibitory effect at an unidentified site in the spleen rather than acting directly on lymphocytes. This report describes the in vivo site of action of mannan. In vivo localization studies with fluoresceinated preparations of mannan (Fl-mannan) and a mannose-6-phosphate-containing yeast phosphomannan monoester core from P. holstii exopolysaccharide (Fl-PPME) demonstrated that the polysaccharide specifically localize in the splenic marginal sinuses in cells with a dendritic morphology termed splenic sinusoidal cells (SSC). Uptake of the polysaccharides by SSC was mediated by a mannan-specific receptor which was saturable and of high avidity. Several lines of evidence suggested that mannan uptake by SSC inhibited splenic entry of lymphocytes. First, the ability of SSC to bind Fl-mannan and Fl-PPME closely paralleled the ability of these polysaccharides to inhibit splenic entry of lymphocytes. In fact, doses of mannan and PPME which would saturate SSC mannan receptors completely blocked splenic entry of lymphocytes. Second, SSC are situated at the initial entry point of lymphocytes into spleen and passage of lymphocytes through the SSC region of spleen was profoundly inhibited by mannan. Finally, direct evidence for adhesion between lymphocytes and SSC was obtained with spleen cell suspensions where clustering between Fl-mannan labeled SSC and lymphocytes was observed. Collectively, these data indicate that mannan (and PPME) inhibit splenic entry of lymphocytes by interacting with SSC, cell which play a critical role in the entry of lymphocytes into the spleen. Whether mannan-specific receptors on SSC directly mediate lymphocyte-SSC adhesion or play on indirect role in modifying lymphocyte migration requires further investigation.