Sulfation-dependent recognition of high endothelial venules (HEV)-ligands by L-selectin and MECA 79, and adhesion-blocking monoclonal antibody

J Exp Med. 1994 Dec 1;180(6):2219-26. doi: 10.1084/jem.180.6.2219.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies
  • Antibodies, Monoclonal / pharmacology*
  • Antigens, CD / immunology
  • Antigens, CD / physiology
  • Antigens, CD34
  • Binding Sites
  • Cell Adhesion / drug effects
  • Cell Adhesion / immunology
  • Cell Adhesion / physiology*
  • Cell Adhesion Molecules / pharmacology*
  • Cells, Cultured
  • Endothelium, Vascular / physiology*
  • Galactose / metabolism
  • L-Selectin
  • Lymph Nodes / blood supply
  • Lymphocytes / physiology*
  • Mice
  • Mice, Inbred ICR
  • Molecular Sequence Data
  • Mucins / immunology
  • Mucins / physiology
  • Peptides / chemical synthesis
  • Peptides / immunology
  • Recombinant Fusion Proteins / pharmacology
  • Sulfates / metabolism*
  • Sulfur Radioisotopes
  • Tritium

Substances

  • Antibodies
  • Antibodies, Monoclonal
  • Antigens, CD
  • Antigens, CD34
  • Cell Adhesion Molecules
  • Mucins
  • Peptides
  • Recombinant Fusion Proteins
  • Sulfates
  • Sulfur Radioisotopes
  • Tritium
  • L-Selectin
  • sulfated glycoprotein p50
  • Galactose