SELECTIVE MODULATION OF THE EXPRESSION OF L-SELECTIN LIGANDS BY AN IMMUNE-RESPONSE

Background: The adhesion molecule L-selectin is expressed on the cell surface of lymphocytes and mediates their migration from the bloodstre am into lymph nodes. L-selectin is able to recognize four glycoprotein ligands, three of which - Sgp50, Sgp90 and Sgp200 - are sulphated, bi nd specifically to L-selectin and are synthesized by the high endothel ial venules of the peripheral and mesenteric lymph nodes. One of these three sulphated L-selectin ligands, Sgp90, has been shown to be ident ical to the known surface marker CD34 and is expressed on the cell sur face of endothelial cells. The cDNA encoding Sgp50 has been cloned, an d its product, which has been designated GlyCAM-1, is secreted. The th ird ligand, Sgp200, is both secreted and cell-associated. We have inve stigated how the expression of these sulphated glycoproteins is regula ted during an immune response. Results: Here we demonstrate that, duri ng a primary immune response, the expression and secretion of both Gly CAM-1 and Sgp200 are reduced, recovering to normal levels 7-10 days af ter antigen stimulation. In contrast, the expression of cell-associate d CD34 and Sgp200 is relatively unaffected. These results may account for the modest decreases in the binding of an L-selectin-IgG fusion pr otein to high endothelial venules of inflamed peripheral lymph nodes t hat have been observed after antigen exposure. In vivo experiments sho w that, following the decrease in the levels of secreted GlyCAM-1 and Sgp200, migration of lymphocytes from the blood stream into lymph node s remains L-selectin-dependent, but more lymphocytes home to antigen-p rimed than unprimed peripheral lymph nodes. Conclusions: We suggest th at the secreted forms of the L-selectin ligands GlyCAM-1 and Sgp200 ac t as modulators of cell adhesion, and that cell-associated CD34 and Sg p200 are the ligands that mediate the initial loose binding of lymphoc ytes to high endothelial venules.