Lectin-like oxidized LDL receptor-1 is a cell-adhesion molecule involved in endotoxin-induced inflammation.
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 agedapoptotic 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.
Honjo
Megumi
M
Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan.
Nakamura
Kayo
K
Yamashiro
Kenji
K
Kiryu
Junichi
J
Tanihara
Hidenobu
H
McEvoy
Leslie M
LM
Honda
Yoshihito
Y
Butcher
Eugene C
EC
Masaki
Tomoh
T
Sawamura
Tatsuya
T
D000818:Animals; D017209:Apoptosis; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D004731:Endotoxins / Q000378:metabolism*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D007150:Immunohistochemistry; D007249:Inflammation; D007962:Leukocytes / Q000166:cytology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism; D018715:Microscopy, Video; D051381:Rats; D011917:Rats, Inbred Lew; D011973:Receptors, LDL / Q000378:metabolism / Q000502:physiology*; D051131:Receptors, Oxidized LDL; D012160:Retina / Q000166:cytology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051127:Scavenger Receptors, Class E; D013997:Time Factors
D015815:Cell Adhesion Molecules; D004731:Endotoxins; D007074:Immunoglobulin G; D008070:Lipopolysaccharides; C495137:OLR1 protein, human; C495136:OLR1 protein, rat; D011973:Receptors, LDL; D051131:Receptors, Oxidized LDL; D051127:Scavenger Receptors, Class E