An In Vitro Model of Cell-Cell Interactions during Lymphocyte Recirculation
Ross, Theodora S.
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Lymphocytes migrate from the blood stream into the lymph nodes and Peyer's Patches across a specialized microvascular network, the post capillary high endothelial venules (HEVs). This movement distributes lymphocytes throughout the lymph and blood, which is necessary for an efficient immunological surveillance of the body. The first step in this directed movement of lymphocytes, termed "recirculation," involves the specific adhesion of the cells to the HEV and not to other vascular endothelia. Although the molecular basis of this selectivity is unknown, recently Stoolman et ale (1983, 1984) have reported evidence that suggests lymphocytes have surface carbohydrate binding proteins (membrane lectins) which recognize and attach to specific carbohydrates on the surface of the HEVs. This study involved the development of a novel in vitro system that provides a well-controlled experimental approach for studying the carbohydrate specificity of the putative membrane lectins. Polymers of carbohydrates were immobilized by entrapping them in polyacrylamide gels. Lymphocytes were then incubated on the gels, the gels inverted, subjected to the desired centrifugal force, and then assayed for specific cellular binding to the immobilized polysaccharide. It was observed that more than 50% of the added cervical lymph node lymphocytes bind to fucoidin but not to mannan, dextran or PPME (a phosphomannosyl core polysaccharide from the yeast Hansenula holstii). Furthermore, fucoidin and D-mannose-6-phosphate were potent inhibitors of cellular attachment to immobilized fucoidin. Since fucoidin and D-mannose-6-phosphate are also potent inhibitors of the binding of lymphocytes to frozen sections of lymph node HEVs, these data suggests that cell surface carbohydrates (fucose-like) and lectins (fucose-specific) may be responsible for the first step in the specific migration of lymphocytes through the HEVs.