Attenuation of rodent lung ischemia-reperfusion injury by sphingosine 1-phosphate

Objective. Lung ischemia-reperfusion (IR) injury, a sequela of transplantation characterized by alveolar damage, edema and inflammation in donor lungs, remains a significant cause of transplant failure despite improvements in lung preservation techniques. We investigated the effects of sphingosine 1-phosphate (S1P), a potent vascular barrier-protective agent, in a rat model of IR injury. Material and methods. S1P (26.5 mg/kg, i.v.) or vehicle was administered 15 min prior to ischemia via pulmonary artery ligation (1 h) and subsequent reperfusion (2 h). Lung vascular permeability and inflammation were assessed. Results. Animals pretreated with S1P exhibited reduced bronchoalveolar lavage (BAL) inflammatory cells (32% decrease; p<0.05), BAL neutrophils (63% decrease; p<0.04), and BAL albumin content (57% decrease; p<0.04) compared to controls. Lung myeloperoxidase activity, an index of parenchymal leukocyte infiltration, was also attenuated in S1P-treated animals (63% decrease; p<0.05). Finally, consistent with the pronounced anti-inflammatory effects of S1P, BAL fluid from animals pretreated with S1P was notable for decreased levels of IL-6 (48% decrease; p<0.01), IL-1β (58% decrease; p<0.05), and IL-2 (92% decrease; p<0.001). Conclusion. Our findings suggest that S1P reduces IR injury and may serve as an effective adjunct to lung preservation strategies prior to transplantation.