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

• DOI: 10.1073/pnas.0337528100
• Publication Date: 2003-02-04T17:24:41Z
• Authors: Megumi Honjo; Kayo Nakamura; Kenji Yamashiro; Junichi Kiryu; Hidenobu Tanihara; Leslie M. McEvoy; Yoshihito Honda; Eugene C. Butcher; Tomoh Masaki; Tatsuya Sawamura
• Keywords: Inflammation; Lipopolysaccharides; 0301 basic medicine; Microscopy, Video; Reverse Transcriptase Polymerase Chain Reaction; Apoptosis; Scavenger Receptors, Class E; Immunohistochemistry; Retina; Rats; Endotoxins; Receptors, Oxidized LDL; 03 medical and health sciences; Receptors, LDL; Rats, Inbred Lew; Immunoglobulin G; Cell Adhesion; Leukocytes; Animals; Humans; Female; Cell Adhesion Molecules

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.