Role of nitric oxide derived from alveolar macrophages in the early phase of acute pancreatitis.
BACKGROUND
Acute pancreatitis is known to be often complicated by lung injury; however, the pathogenesis of lung injury in the early phase of acute pancreatitis remains unclear. Alveolar macrophages (AMs) have been suggested to contribute to lung injury by releasing various cytotoxic products including nitric oxide (NO). We investigated the role of AM-derived NO in the pathogenesis of lung injury during the early phase of acute pancreatitis.


METHODS
Pancreatitis was induced in rats by selective pancreatic duct ligation (SPL). The mRNA expression of inducible NO synthase (iNOS) in AMs from rats after SPL (at 1, 2, 4, 6, 8, 12, 18, and 24 hr) was examined by reverse-transcriptase polymerase chain reaction method. The in vitro production of NO and superoxide by AMs 24 hr after SPL was measured and the cytotoxic effect of AMs on human umbilical vein endothelial cells (HUVECs) was examined with or without the NO synthase inhibitor L-NG-monomethyl-L-arginine (L-NMMA). The in vivo effect of L-NMMA on lung injury was also examined.


RESULTS
In this model, serum amylase level peaked 24 hr after SPL, whereas PaO2 bottomed 24 hr after SPL. (In vitro) AMs expressed iNOS mRNA 6 hr after SPL and generated large amounts of NO and superoxide and demonstrated strong cytotoxicity against HUVECs significantly. This cytotoxicity was reduced by the administration of L-NMMA. (In vivo) L-NMMA administrated to rats with pancreatitis apparently reduced lung edema histologically and improved the PaO2.


CONCLUSIONS
Our results suggest that, during early phase of acute pancreatitis, AM-derived NO contributes to lung injury. Administration of the NOS inhibitor L-NMMA prevented lung injury in this model.
Tsukahara
Y
Y
Division of Clinical Immunology, Kyushu University, Fukuoka, Japan.
Horita
Y
Y
Anan
K
K
Morisaki
T
T
Tanaka
M
M
Torisu
M
M
D000208:Acute Disease; D000818:Animals; D016676:Macrophages, Alveolar / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010195:Pancreatitis / Q000209:etiology*; D051381:Rats; D017208:Rats, Wistar; D012128:Respiratory Distress Syndrome / Q000209:etiology; D013481:Superoxides / Q000378:metabolism; D019323:omega-N-Methylarginine / Q000494:pharmacology
D013481:Superoxides; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase