Sphingosine-1-phosphate and its analogue FTY720 diminish acute pulmonary injury in rats with acute necrotizing pancreatitis.
OBJECTIVE
To investigate the effects of sphingosine-1-phosphate (S1P) and its analogue FTY720 on the lung injury induced by acute necrotizing pancreatitis in rats.


METHODS
Acute necrotizing pancreatitis was induced by retrogradely injection of 5% sodium taurocholate of biliopancreatic duct in rats. Sphingosine-1-phosphate (100 microg/kg) or FTY720 (1 mg/kg) was administered immediately after the model induction by peritoneal injection. Six hours after the model induction, bronchoalveolar lavage protein concentration, total cell count, polymorphonuclear neutrophil percentage, proinflammatory cytokines (interleukin 1beta, interleukin 6, and tumor necrosis factor alpha), nuclear factor kappaB activation of alveolar macrophages, and lung myeloperoxidase (MPO) activity were examined. Serum amylase and lipase were tested. In addition, histopathological changes of the pancreas and lung were observed.


RESULTS
Bronchoalveolar lavage protein concentration, total cell count, PMN percentage, proinflammatory cytokines, nuclear factor kappaB activation, lung capillary leakage, and lung myeloperoxidase were all reduced significantly in both S1P and FTY720 groups. The pulmonary pathological injury in both S1P and FTY720 groups was ameliorated obviously. Nevertheless, the serum amylase, lipase, and the pancreatic pathological damages were not decreased.


CONCLUSIONS
Sphingosine-1-phosphate and its analogue FTY720 significantly decreased pulmonary inflammation and injury in a rat model of acute lung injury caused by acute necrotizing pancreatitis and may represent a novel therapeutic strategy for the acute necrotizing pancreatitis-associated lung injury.
Liu
Hong-Bin
HB
Department of Pharmacology, Tianjin Institute of Acute Abdominal Diseases, Tianjin, China. jtsstj1@yahoo.com.cn
Cui
Nai-Qiang
NQ
Wang
Qian
Q
Li
Dong-Hua
DH
Xue
Xiao-Ping
XP
D000681:Amylases / Q000097:blood; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D002199:Capillary Permeability / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D000068876:Fingolimod Hydrochloride; D008049:Lipase / Q000097:blood; D008168:Lung / Q000098:blood supply / Q000187:drug effects* / Q000503:physiopathology; D055370:Lung Injury; D008246:Lysophospholipids / Q000627:therapeutic use*; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D019283:Pancreatitis, Acute Necrotizing / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D009195:Peroxidase / Q000378:metabolism; D011409:Propylene Glycols / Q000627:therapeutic use*; D011654:Pulmonary Edema / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control; D051381:Rats; D017208:Rats, Wistar; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000627:therapeutic use
D016207:Cytokines; D008246:Lysophospholipids; D016328:NF-kappa B; D011409:Propylene Glycols; C060506:sphingosine 1-phosphate; D009195:Peroxidase; D008049:Lipase; D000681:Amylases; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine