Effect of sulfatide on acute lung injury during endotoxemia in rats

Experimental studies have shown that intrapulmonary leukocyte sequestration and activation is implicated in the pathogenesis of acute lung injury duri ng endotoxemia. Selectins are involved in the adhesion of leukocyte to the endothelium. Sulfatide is recognized by P selectin and blocks this adhesion molecule. We studied the effects of sulfatide on endotoxin-induced lung da mage in rats. Endotoxin shock was produced in male rats by a single intrave nous (i.v.) injection of 20 mg/kg of Salmonella enteritidis lipopolysacchar ide (LPS). LPS administration reduced survival rate (0%, 72 h after endotox in challenge) decreased mean arterial blood pressure (MAP), produced leukop enia (Controls=11,234 +/- 231 cells/mL, LPS=4,567 +/- 123 cells/mL) and inc reased lung myeloperoxidase activity (MPO; a marker of leukocyte accumulati on) in the lung (Controls =0.35 +/- 0.1 U/g/tissue; LPS= 10 +/- 1.2 U/g/tis sue). Furthermore LPS administration markedly impaired the concentration-re sponse curves for acetylcholine and sodium nitroprusside in isolated polmon ary arterial rings. There was also an increased staining for P-selectin in the pulmonary arteries. Sulfatide treatment (10 mg/kg, 30 min. after LPS ch allenge), significantly protected against LPS-induced lethality (90% surviv al rate and 70% survival rate 24 h and 72 h after LPS injection), reduced L PS induced hypothension, reverted leukopenia (8,895 +/- 234 cells/ml) and l owered lung MPO activity (1.7 +/- 0.9 U/g/tissue). Furthermore sulfatide re stored to control values the LPS-induced impairment in arterial pulmonary v asorelaxation and reduced P-selectin immunostaining. Our data indicate that sulfatide attenuates LPS-induced lung injury and protects against endotoxi n shock.