L- and E-selectin can recognize the same naturally occurring ligands on high endothelial venules.
The selectin family of cell adhesion molecules consists of three members, E-selectin (ELAM-1), L-selectin (LECAM-1), and P-selectin (CD62, GMP140, or PADGEM), which are all involved in binding of leukocytes to endothelial cells. All members have structural similarities and they can all bind to a common carbohydrate epitope, sialyl Lewis X in in vitro assays. To study cross-reactivity of the selectins in more detail we used Ig chimeras of murine and human L- and human E-selectin. All three 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- and 90-kDa sulfated ligands from organ cultures of murine peripheral and mesenteric lymph nodes. This recognition was calcium dependent and inhibitable by mAb specific for the lectin domain of the respective selectin. L- and E-selectin binding to high endothelial venules and to the sulfated ligands was inhibitable by the carbohydrates, fucoidan and sialyl 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 inhibit in vivo lymphocyte trafficking into peripheral lymph nodes equally well.
Mebius
R E
RE
Department of Pathology, Stanford University, Palo Alto, CA 94305.
Watson
S R
SR
D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D019040:E-Selectin; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D006801:Humans; D019041:L-Selectin; D016256:Lewis X Antigen / Q000378:metabolism; D008024:Ligands; D008198:Lymph Nodes / Q000378:metabolism; D008214:Lymphocytes / Q000166:cytology*; D051379:Mice; D014066:Palatine Tonsil / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism
D015815:Cell Adhesion Molecules; D019040:E-Selectin; D016256:Lewis X Antigen; D008024:Ligands; D011993:Recombinant Fusion Proteins; D019041:L-Selectin