Collagen XVIII, a Basement Membrane Heparan Sulfate Proteoglycan, Interacts with L-selectin and Monocyte Chemoattractant Protein-1

• Published in: The Journal of biological chemistry 2003-04, Vol.278 (15), p.13069-13076
• Main Authors: Kawashima, Hiroto, Watanabe, Norifumi, Hirose, Mayumi, Sun, Xin, Atarashi, Kazuyuki, Kimura, Tetsuya, Shikata, Kenichi, Matsuda, Mitsuhiro, Ogawa, Daisuke, Heljasvaara, Ritva, Rehn, Marko, Pihlajaniemi, Taina, Miyasaka, Masayuki
• Format: Article
• Language: English
• Subjects: 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
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M212244200

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 α 4 β 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.