L-SELECTIN AND E-SELECTIN CAN RECOGNIZE THE SAME NATURALLY-OCCURRING LIGANDS ON HIGH ENDOTHELIAL VENULES

The selectin family of cell adhesion molecules consists of three membe rs, E-selectin (ELAM-1), L-selectin (LECAM-1), and P-selectin (CD62, G MP140, or PADGEM), which are all involved in binding of leukocytes to endothelial cells. All members have structural similarities and they c an all bind to a common carbohydrate epitope, sialyl Lewis X in in vit ro assays. To study cross-reactivity of the selectins in more detail w e used Ig chimeras of murine and human L- and human E-selectin. All th ree chimeras bound to the natural ligands of L-selectin on specialized high endothelial venules in both human and murine lymphoid organs as determined by immunohistochemistry and were able to precipitate 50- an d 90-kDa sulfated ligands from organ cultures of murine peripheral and mesenteric lymph nodes. This recognition was calcium dependent and in hibitable by mAb specific for the lectin domain of the respective sele ctin. L- and E-selectin binding to high endothelial venules and to the sulfated ligands was inhibitable by the carbohydrates, fucoidan and s ialyl Lewis X, respectively. Although immunoprecipitations showed that both murine and human L-selectin could recognize the sulfated ligands from high endothelial venules more efficiently than human E-selectin at the concentrations used, both L- and E-selectin chimeras could inhi bit in vivo lymphocyte trafficking into peripheral lymph nodes equally well.