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 during 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 damage in rats. Endotoxin shock was produced in male rats by a single intravenous (i.v.) injection of 20 mg/kg of Salmonella enteritidis lipopolysaccharide (LPS). LPS administration reduced survival rate (0%, 72 h after endotoxin challenge) decreased mean arterial blood pressure (MAP), produced leukopenia (Controls = 11,234+/-231 cells/mL, LPS = 4,567+/-123 cells/mL) and increased lung myeloperoxidase activity (MPO; a marker of leukocyte accumulation) in the lung (Controls = 0.35+/-0.1 U/g/tissue; LPS = 10+/-1.2 U/g/tissue). Furthermore LPS administration markedly impaired the concentration-response curves for acetylcholine and sodium nitroprusside in isolated pulmonary arterial rings. There was also an increased staining for P-selectin in the pulmonary arteries. Sulfatide treatment (10 mg/kg, 30 min. after LPS challenge), significantly protected against LPS-induced lethality (90% survival rate and 70% survival rate 24 h and 72 h after LPS injection), reduced LPS induced hypotension, reverted leukopenia (8,895+/-234 cells/ml) and lowered lung MPO activity (1.7+/-0.9 U/g/tissue). Furthermore sulfatide restored to control values the LPS-induced impairment in arterial pulmonary vasorelaxation and reduced P-selectin immunostaining. Our data indicate that sulfatide attenuates LPS-induced lung injury and protects against endotoxin shock.
Squadrito
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Institute of Pharmacology, School of Medicine, University of Messina, Italy. squadrito@csnet.it
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Arlotta
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Minutoli
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AP
D000208:Acute Disease; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000378:metabolism; D019446:Endotoxemia / Q000473:pathology*; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects* / Q000473:pathology*; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009599:Nitroprusside / Q000494:pharmacology; D019007:P-Selectin / Q000276:immunology / Q000378:metabolism; D011651:Pulmonary Artery / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013433:Sulfoglycosphingolipids / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D019007:P-Selectin; D013433:Sulfoglycosphingolipids; D009599:Nitroprusside