Protective effect of anti-P-selectin monoclonal antibody in lipopolysaccharide-induced lung hemorrhage.
Excessive leukocyte accumulation is involved in the pathogenesis of the sepsis-induced acute lung injury. Selectins are essential to the interaction between leukocytes and endothelial cells. In this report, we investigated the role of selectins in the severe lung injury induced by lipopolysaccharide (LPS). Significant lung hemorrhage was observed 24 h after the intravenous administration of LPS (1 mg/kg). First, we evaluated the effect of sialyl Lewis X-oligosaccharide (SLeX-OS), a derivative of sialyl Lewis X which is one of the ligands for E-, P- and L-selectins. The treatment with SLeX-OS (26.5 mg/kg iv bolus + 19.8 mg/kg iv infusion) resulted in a decrease of lung hemorrhage by 49.5% (P<0.05 versus the control group). Second, we tested the effect of anti-P-selectin monoclonal antibody (MAb), PB 1.3, to investigate the role of P-selectin. The bolus administration of PB1.3 at a dose of 5 mg/kg attenuated the lung hemorrhage by 74.6% (P<0.05 versus the control group). In addition, we also detected an increase of soluble P-selectin in plasma 24 h after the injection of LPS. These results suggest that P-selectin has a substantial role in the pathogenesis of the lung injury induced by LPS.
Ohnishi
M
M
Sumitomo Pharmaceuticals Research Center, Osaka, Japan.
Imanishi
N
N
Tojo
S J
SJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology* / Q000627:therapeutic use*; D006470:Hemorrhage / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D008070:Lipopolysaccharides / Q000633:toxicity; D008168:Lung / Q000503:physiopathology*; D008297:Male; D019007:P-Selectin / Q000276:immunology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000911:Antibodies, Monoclonal; D008070:Lipopolysaccharides; D019007:P-Selectin