Collagen XVIII, a basement membrane heparan sulfate proteoglycan, interacts with L-selectin and monocyte chemoattractant protein-1.
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.
Kawashima
Hiroto
H
Laboratory of Molecular and Cellular Recognition, Osaka University Graduate School of Medicine, 2-2, Yamada-oka, Suita 565-0871, Japan. hkawashima@burnham.org
Watanabe
Norifumi
N
Hirose
Mayumi
M
Sun
Xin
X
Atarashi
Kazuyuki
K
Kimura
Tetsuya
T
Shikata
Kenichi
K
Matsuda
Mitsuhiro
M
Ogawa
Daisuke
D
Heljasvaara
Ritva
R
Rehn
Marko
M
Pihlajaniemi
Taina
T
Miyasaka
Masayuki
M
D000595:Amino Acid Sequence; D000818:Animals; D001485:Basement Membrane / Q000502:physiology*; D001665:Binding Sites; D018932:Chemokine CCL2 / Q000378:metabolism*; D003094:Collagen / Q000378:metabolism*; D043170:Collagen Type XVIII; D004492:Edetic Acid / Q000494:pharmacology; D043169:Endostatins; D006801:Humans; D007668:Kidney / Q000378:metabolism; D007700:Kinetics; D019041:L-Selectin / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D011133:Polysaccharide-Lyases / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection
D018932:Chemokine CCL2; D043170:Collagen Type XVIII; D043169:Endostatins; D010446:Peptide Fragments; D011994:Recombinant Proteins; D019041:L-Selectin; D003094:Collagen; D004492:Edetic Acid; D011133:Polysaccharide-Lyases; C021349:heparitinsulfate lyase