Lectin-like oxidized LDL receptor-1 is a cell-adhesion molecule involved in endotoxin-induced inflammation

被引:132
作者
Honjo, M
Nakamura, K
Yamashiro, K
Kiryu, J
Tanihara, H
McEvoy, LM
Honda, Y
Butcher, EC
Masaki, T
Sawamura, T [1 ]
机构
[1] Natl Cardiovasc Ctr, Res Inst, Dept Biosci, Suita, Osaka 5658565, Japan
[2] Kyoto Univ, Grad Sch Med, Dept Ophthalmol & Visual Sci, Kyoto 6068507, Japan
[3] Kumamoto Univ, Sch Med, Dept Ophthalmol, Kumamoto 8608556, Japan
[4] Corgentech Inc, Palo Alto, CA 94304 USA
[5] Stanford Univ, Sch Med, Dept Pathol, Palo Alto, CA 94304 USA
关键词
D O I
10.1073/pnas.0337528100
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 [理学]; 0710 [生物学]; 09 [农学];
摘要
Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is a major endothelial receptor for oxidized low-density lipoprotein, and is assumed to play a proatherogenic role in atherosclerosis. LOX-1 expression is induced by inflammatory cytokines as well as by proatherogenic stimuli. LOX-1 protein binds aged/apoptotic cells, activated platelets, and bacteria, suggesting that it may have diverse activities in vivo. Here, we reveal a role for LOX-1 in endotoxin-induced inflammation. In a model of endotoxemia, injection of a high dose of endotoxin into rats induced leukopenia within 1 h and death of the animals within 24 h. Preadministration of anti-LOX-1 antibody reduced the degree of leukopenia and completely rescued the animals, whereas control IgG did not. In a model of low-dose endotoxin-induced uveitis, anti-LOX-1 antibody efficiently suppressed leukocyte infiltration and protein exudation. In situ videomicroscopic analyses of leukocyte interactions with retinal veins revealed that anti-LOX-1 antibody reduced the number of rolling leukocytes and increased the velocity of rolling, suggesting that LOX-1 functions as a vascular tethering ligand. The ability of LOX-1 to capture leukocytes under physiologic shear was confirmed in an in vitro flow model. Thus, LOX-1 is an adhesion molecule involved in leukocyte recruitment and may represent an attractive target for modulation of endotoxin-induced inflammation.
引用
收藏
页码:1274 / 1279
页数:6
相关论文
共 32 条
[1]
Structure and chromosomal assignment of the human lectin-like oxidized low-density-lipoprotein receptor-1 (LOX-1) gene [J].
Aoyama, T ;
Sawamura, T ;
Furutani, Y ;
Matsuoka, R ;
Yoshida, MC ;
Fujiwara, H ;
Masaki, T .
BIOCHEMICAL JOURNAL, 1999, 339 :177-184
[2]
Induction of lectin-like oxidized LDL receptor by oxidized LDL and lysophosphatidylcholine in cultured endothelial cells [J].
Aoyama, T ;
Fujiwara, H ;
Masaki, T ;
Sawamura, T .
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 1999, 31 (12) :2101-2114
[3]
The centromeric part of the human NK gene complex:: linkage of LOX-1 and LY49L with the CD94/NKG2 region [J].
Bull, C ;
Sobanov, Y ;
Röhrdanz, B ;
O'Brien, J ;
Lehrach, H ;
Hofer, E .
GENES AND IMMUNITY, 2000, 1 (04) :280-287
[4]
Lymphocyte trafficking and regional immunity [J].
Butcher, EC ;
Williams, M ;
Youngman, K ;
Rott, L ;
Briskin, M .
ADVANCES IN IMMUNOLOGY, VOL. 72, 1999, 72 :209-253
[5]
Upregulation of LOX-1 expression in aorta of hypercholesterolemic rabbits: Modulation by losartan [J].
Chen, H ;
Li, D ;
Sawamura, T ;
Inoue, K ;
Mehta, JL .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2000, 276 (03) :1100-1104
[6]
Increased expression of lectinlike oxidized low density lipoprotein receptor-1 in initial atherosclerotic lesions of Watanabe heritable hyperlipidemic rabbits [J].
Chen, MY ;
Kakutani, M ;
Minami, M ;
Kataoka, H ;
Kume, N ;
Narumiya, S ;
Kita, T ;
Masaki, T ;
Sawamura, T .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2000, 20 (04) :1107-1115
[7]
Diabetes enhances lectin-like oxidized LDL receptor-1 (LOX-1) expression in the vascular endothelium: Possible role of LOX-1 ligand and AGE [J].
Chen, MY ;
Nagase, M ;
Fujita, T ;
Narumiya, S ;
Masaki, T ;
Sawamura, T .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2001, 287 (04) :962-968
[8]
Requirements of basic amino acid residues within the lectin-like domain of LOX-1 for the binding of oxidized low-density lipoprotein [J].
Chen, MY ;
Inoue, K ;
Narumiya, S ;
Masaki, T ;
Sawamura, T .
FEBS LETTERS, 2001, 499 (03) :215-219
[9]
Conserved C-terminal residues within the lectin-like domain of LOX-1 are essential for oxidized low-density-lipoprotein binding [J].
Chen, MY ;
Narumiya, S ;
Masaki, T ;
Sawamura, T .
BIOCHEMICAL JOURNAL, 2001, 355 :289-296
[10]
The binding of oxidized low density lipoprotein (ox-LDL) to ox-LDL receptor-1 reduces the intracellular concentration of nitric oxide in endothelial cells through an increased production of superoxide [J].
Cominacini, L ;
Rigoni, A ;
Fratta Pasini, A ;
Garbin, U ;
Davoli, A ;
Campagnola, R ;
Pastorino, AM ;
Lo Cascio, V ;
Sawamura, T .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (17) :13750-13755