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

The prophylactic effects of selectin inhibitors on lipopolysaccharide-induc ed acute lung injury were studied in rabbits by using sialyl Lewis X-oligos accharide and PB1.3, an anti-human P-selectin monoclonal antibody. Lipopoly saccharide-induced acute lung injury resembles that of the acute respirator y distress syndrome, in which there is a decrease in arterial blood oxygen tension (PaO2) and an increase in the difference between alveolar and arter ial oxygen tension (A-aDO(2)). Prophylactic treatment with the selectin inh ibitors, 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 immediate ly before lipopolysaccharide administration), prevented the lipopolysacchar ide-induced impairments in pulmonary gas exchange. In contrast, these agent s had no significant effects on lipopolysaccharide-induced systemic hypoten sion, the decrease in the number of circulating white blood cells and plate lets, the decline in blood pH, or the increase in arterial CO2 tension (PaC O2). These results indicate that selectin inhibitors including sialyl Lewis X-oligosaccharide and the anti-P-selectin antibody, PB1.3, attenuate lipop olysaccharide-induced acute lung injury in rabbits. This is the first demon stration that P-selectin is directly involved in the development of lipopol ysaccharide-induced impairments in pulmonary gas exchange. (C) 1999 Elsevie r Science B.V. All rights reserved.