Collagen XVIII, a basement membrane heparan sulfate proteoglycan, interacts with L-selectin and monocyte chemoattractant protein-1

J Biol Chem. 2003 Apr 11;278(15):13069-76. doi: 10.1074/jbc.M212244200. Epub 2003 Jan 28.

Abstract

Leukocyte infiltration during inflammation is mediated by the sequential actions of adhesion molecules and chemokines. By using a rat ureteral obstruction model, we showed previously that L-selectin plays an important role in leukocyte infiltration into the kidney. Here we report the purification, identification, and characterization of an L-selectin-binding heparan sulfate proteoglycan (HSPG) expressed in the rat kidney. Partial amino acid sequencing and Western blotting analyses showed that the L-selectin-binding HSPG is collagen XVIII, a basement membrane HSPG. The binding of L-selectin to isolated collagen XVIII was specifically inhibited by an anti-L-selectin monoclonal antibody, EDTA, treatment of the collagen XVIII with heparitinase or heparin but not by chemically desulfated heparin. A cell binding assay showed that the L-selectin-collagen XVIII interaction mediates cell adhesion. Interestingly, collagen XVIII also interacted with a chemokine, monocyte chemoattractant protein-1, and presented it to a monocytic cell line, THP-1, which enhanced the alpha(4)beta(1) integrin-mediated binding of the THP-1 cells to vascular cell adhesion molecule-1. Thus, collagen XVIII may provide a link between selectin-mediated cell adhesion and chemokine-induced cellular activation and accelerate the progression of leukocyte infiltration in renal inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Basement Membrane / physiology*
  • Binding Sites
  • Chemokine CCL2 / metabolism*
  • Collagen / metabolism*
  • Collagen Type XVIII
  • Edetic Acid / pharmacology
  • Endostatins
  • Humans
  • Kidney / metabolism
  • Kinetics
  • L-Selectin / metabolism*
  • Peptide Fragments / metabolism*
  • Polysaccharide-Lyases / metabolism
  • Rats
  • Recombinant Proteins / metabolism
  • Transfection

Substances

  • Chemokine CCL2
  • Collagen Type XVIII
  • Endostatins
  • Peptide Fragments
  • Recombinant Proteins
  • L-Selectin
  • Collagen
  • Edetic Acid
  • Polysaccharide-Lyases
  • heparitinsulfate lyase