Previous in vitro studies suggest that recognition of phosphomannosyl structures by lymphocytes plays a central role in the binding of lymphocytes to high endothelial venules. However, the physiologic relevance of phosphomannosyl recognition in in vivo lymphocyte migration has not been established. This paper describes experiments that examined this question. It was demonstrated that the phosphomannan monoester core (PPME) from Pichia holstii, a potent inhibitor of peripheral node high endothelial venule interactions in vitro, was a very effective inhibitor of in vivo lymphocyte migration, as little as 39 micrograms/mouse significantly inhibiting popliteal lymph node entry. Furthermore, PPME exhibited a similar hierarchy of inhibition in vivo as previously reported in vitro, most effectively inhibiting entry of lymphocytes into popliteal lymph node, somewhat less effectively inhibiting mesenteric lymph node entry and being a relatively poor inhibitor of Peyer's patch entry. Additionally, PPME inhibited splenic entry of lymphocytes, and inhibition of lymphoid organ entry was accompanied by a substantial leukocytosis. Two additional mannose-containing compounds were found to modify lymphocyte migration, namely a well defined mannose containing pentasaccharide (PENT) with terminal mannose-6-phosphate (M6P) and an unphosphorylated yeast mannan. Both PENT and mannan induced leukocytosis and were particularly effective at inhibiting splenic entry of lymphocytes. In fact, detailed dose-response curves indicated that mannan was a much more potent inhibitor of splenic entry than PPME or PENT, whereas in lymph nodes PPME was the most effective inhibitor. Pretreatment of lymphocytes before injection with either PPME or mannan demonstrated that PPME could act at the lymphocyte level, whereas mannan probably acted at some other site. Collectively, these data suggest that different carbohydrate structures are involved in the entry of lymphocytes into different lymphoid organs, with mannose recognition playing an important role in splenic entry and recognition of M6P-like structures controlling lymph node entry. In contrast, it was found that mannose-and M6P-containing structures, unlike sulfated polysaccharides such as fucoidan, did not affect the subsequent positioning of lymphocytes within lymphoid organs.

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