RECEPTORS INVOLVED IN CARBOHYDRATE-BINDING MODULATE INTESTINAL EPITHELIAL-NEUTROPHIL INTERACTIONS

Neutrophil (polymorphonuclear neutrophil) migration across epithelial barriers is a common morphologic feature of many diseases. Previous st udies show that PMN-epithelial interactions are dependent on the PMN b eta(2)-integrin CD11b/18; however, nothing is known about surface carb ohydrates and PMN epithelial interactions. Here we investigate the rol e of carbohydrates on PMN-epitehlial interactions using PMN and cultur ed monolayers of the intestinal epithelial cell line T84. Addition of the carbohydrates mannose 6-phosphate (Man-6-P) and glucose 6-phosphat e (Glu-6-P), but not fructose 1-phosphate (Fru-1-P) inhibited transmig ration by greater than or equal to 70%. Likewise, more complex carbohy drates, such as fucoidin and the Man-B-6-rich polysaccharide PPME sele ctively inhibited PMN transepithelial migration. These carbohydrates w ere found to be inhibitory in the apical-to-basolateral direction as w ell as the basolateral-to-apical direction, indicating a lack of polar ity. This panel of related carbohydrates, however, was not effective i n modulating short-term adhesion of PMN to epithelial monolayers, indi cating that carbohydrate ligands may modulate different steps in the t ransmigration cascade. Finally, addition of functionally inhibitory mo noclonal antibodies specific for the selectins (CD62E, CD62L, and CD62 P) revealed no observable effect on PMN transmigration. These studies suggest that cell surface carbohydrates may play a role in inflammator y processes of the intestine.