title: Sulfation-dependent recognition of high endothelial venules (HEV)-ligands by L-selectin and MECA 79, and adhesion-blocking monoclonal antibody.
abstract: L-selectin is a lectin-like receptor that mediates the attachment of lymphocytes to high endothelial venules (HEV) of lymph nodes during the process of lymphocyte recirculation. Two sulfated, mucin-like glycoproteins known as Sgp50/GlyCAM-1 and Sgp90/CD34 have previously been identified as HEV-associated ligands for L-selectin. These proteins were originally detected with an L-selectin/Ig chimera called LEC-IgG. GlyCAM-1 and CD34 are also recognized by an antiperipheral node addressin (PNAd) mAb called MECA 79, which blocks L-selectin-dependent adhesion and selectively stains lymph node HEV. The present study compares the requirements for the binding of MECA 79 and LEC-IgG to HEV-ligands. Whereas desialylation of GlyCAM-1 and CD34 drastically reduced binding to LEC-IgG, this treatment enhanced the binding of GlyCAM-1 to MECA 79. In contrast, the binding of both MECA 79 and LEC-IgG to GlyCAM-1 and CD34 was greatly decreased when the sulfation of these ligands was reduced with chlorate, a metabolic inhibitor of sulfation. Because MECA 79 stains HEV-like vessels at various sites of inflammation, recognition by L-selectin of ligands outside of secondary lymphoid organs may depend on sulfation. In addition to their reactivity with GlyCAM-1 and CD34, both MECA 79 and LEC-IgG recognize an independent molecule of approximately 200 kD in a sulfate-dependent manner. Thus, this molecule, which we designate Sgp200, is an additional ligand for L-selectin.
authors.affiliation: Department of Anatomy, University of California, San Francisco 94143-0452.
authors.forename: S
authors.initials: S
authors.lastname: Hemmerich
authors.forename: E C
authors.initials: EC
authors.lastname: Butcher
authors.forename: S D
authors.initials: SD
authors.lastname: Rosen
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D015703:Antigens, CD / Q000276:immunology / Q000502:physiology; D018952:Antigens, CD34; D001665:Binding Sites; D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000494:pharmacology*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000502:physiology*; D005690:Galactose / Q000378:metabolism; D019041:L-Selectin; D008198:Lymph Nodes / Q000098:blood supply; D008214:Lymphocytes / Q000502:physiology*; D051379:Mice; D008813:Mice, Inbred ICR; D008969:Molecular Sequence Data; D009077:Mucins / Q000276:immunology / Q000502:physiology; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D013431:Sulfates / Q000378:metabolism*; D013462:Sulfur Radioisotopes; D014316:Tritium
chemical_list: D000906:Antibodies; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018952:Antigens, CD34; D015815:Cell Adhesion Molecules; D009077:Mucins; D010455:Peptides; D011993:Recombinant Fusion Proteins; D013431:Sulfates; D013462:Sulfur Radioisotopes; D014316:Tritium; D019041:L-Selectin; C075185:sulfated glycoprotein p50; D005690:Galactose