Blockade of LOX-1 prevents endotoxin-induced acute lung inflammation and injury in mice.
Lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (LOX-1), a cell surface receptor expressed in endothelial cells, is known to mediate oxidized LDL-induced vascular inflammation and atherogenesis. Although the role of LOX-1 in vascular inflammation has been well established, its involvement in acute lung inflammation and injury remains unclear. In the present study, we examined the effects of a LOX-1-blocking antibody on lung inflammation in a mouse endotoxin lipopolysaccharide (LPS)-induced acute lung injury model. We demonstrated that intraperitoneal challenge with LPS induced a rapid and robust increase in LOX-1 expression in mouse lung. Pre-treatment of mice with anti-LOX-1-blocking antibody significantly inhibited LPS-induced lung inflammation as indicated by decreased neutrophil accumulation in the lung. Furthermore, anti-LOX-1 was capable of inhibiting LPS-induced inflammatory responses, including NF-kappaB activation, ICAM-1 expression and apoptotic signaling, in mouse lung. Collectively, these results indicate that LOX-1 may serve as a valuable therapeutic target in the prevention of acute lung inflammation and injury in sepsis.
Zhang
Ping
P
Center for Biomedical Research, University of Texas Health Science Center at Tyler, Tyler, TX 75708, USA.
Liu
Ming-Cheh
MC
Cheng
Lili
L
Liang
Mei
M
Ji
Hong-long
HL
Fu
Jian
J
D000818:Animals; D019138:Antibodies, Blocking / Q000627:therapeutic use*; D017209:Apoptosis / Q000276:immunology; D004731:Endotoxins / Q000276:immunology*; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology; D055370:Lung Injury / Q000276:immunology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D011014:Pneumonia / Q000276:immunology / Q000517:prevention & control*; D051127:Scavenger Receptors, Class E / Q000037:antagonists & inhibitors* / Q000276:immunology
D019138:Antibodies, Blocking; D004731:Endotoxins; D008070:Lipopolysaccharides; D016328:NF-kappa B; C495138:Olr1 protein, mouse; D051127:Scavenger Receptors, Class E; D018799:Intercellular Adhesion Molecule-1