Protective effects of sialyl Lewis X and anti-P-selectin antibody against lipopolysaccharide-induced acute lung injury in rabbits

• Published in: European journal of pharmacology 1999-04, Vol.370 (1), p.47-56
• Main Authors: Hayashi, Hirotsugu, Koike, Haruhiko, Kurata, Yukiko, Imanishi, Noriaki, Tojo, Shinichiro J.
• Format: Article
• Language: English
• Subjects: Acute lung injury; Animals; Anti-P-selectin antibody; Antibodies, Monoclonal - therapeutic use; Biological and medical sciences; Blood Pressure - drug effects; Dose-Response Relationship, Drug; Inflammation - drug therapy; Inflammation - etiology; Inflammation - pathology; Injections, Intravenous; Lipopolysaccharide; Lipopolysaccharides - toxicity; Lung Diseases - drug therapy; Lung Diseases - etiology; Lung Diseases - pathology; Male; Medical sciences; Oligosaccharides - therapeutic use; P-Selectin - immunology; Pharmacology. Drug treatments; Pulmonary Gas Exchange - drug effects; Rabbits; Respiratory system; Selectin; Sialyl Lewis X
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(99)00068-0

The prophylactic effects of selectin inhibitors on lipopolysaccharide-induced acute lung injury were studied in rabbits by using sialyl Lewis X-oligosaccharide and PB1.3, an anti-human P-selectin monoclonal antibody. Lipopolysaccharide-induced acute lung injury resembles that of the acute respiratory distress syndrome, in which there is a decrease in arterial blood oxygen tension (PaO 2) and an increase in the difference between alveolar and arterial oxygen tension (A-aDO 2). Prophylactic treatment with the selectin inhibitors, sialyl Lewis X-oligosaccharide (55 mg kg −1 i.v. bolus injection immediately before lipopolysaccharide administration+36 mg kg −1 h −1 i.v. infusion for 4 h) and PB1.3 (5 mg kg −1 i.v. bolus injection immediately before lipopolysaccharide administration), prevented the lipopolysaccharide-induced impairments in pulmonary gas exchange. In contrast, these agents had no significant effects on lipopolysaccharide-induced systemic hypotension, the decrease in the number of circulating white blood cells and platelets, the decline in blood pH, or the increase in arterial CO 2 tension (PaCO 2). These results indicate that selectin inhibitors including sialyl Lewis X-oligosaccharide and the anti-P-selectin antibody, PB1.3, attenuate lipopolysaccharide-induced acute lung injury in rabbits. This is the first demonstration that P-selectin is directly involved in the development of lipopolysaccharide-induced impairments in pulmonary gas exchange.