TY - JOUR
T1 - Attenuation of rodent lung ischemia-reperfusion injury by sphingosine 1-phosphate
AU - Moreno-Vinasco, Liliana
AU - Jacobson, Jeffrey R.
AU - Bonde, Pramod
AU - Sammani, Saad
AU - Mirzapoiazova, Tamara
AU - Vigneswaran, Wickii T.
AU - Garcia, Joe G N
PY - 2008/7/1
Y1 - 2008/7/1
N2 - 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.
AB - 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.
KW - Graft failure
KW - Perfusate
KW - Sphingosine 1-phosphate
KW - Vascular permeability
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U2 - 10.1080/17471060701505289
DO - 10.1080/17471060701505289
M3 - Article
AN - SCOPUS:45849100184
SN - 1747-1060
VL - 4
SP - 106
EP - 114
JO - Journal of Organ Dysfunction
JF - Journal of Organ Dysfunction
IS - 2
ER -