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

Hiroto Kawashima, Norifumi Watanabe, Mayumi Hirose, Xin Sun, Kazuyuki Atarashi, Tetsuya Kimura, Kenichi Shikata, Mitsuhiro Matsuda, Daisuke Ogawa, Ritva Heljasvaara, Marko Rehn, Taina Pihlajaniemi, Masayuki Miyasaka

Research output: Contribution to journalArticle

65 Citations (Scopus)

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 α4β1 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.

Original languageEnglish
Pages (from-to)13069-13076
Number of pages8
JournalJournal of Biological Chemistry
Volume278
Issue number15
DOIs
Publication statusPublished - Apr 11 2003

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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