Oxygen in the alveolar air space mediates lung inflammation in acute pancreatitis.
During the early stages of acute pancreatitis, acute respiratory distress syndrome often occurs. This is associated with the release of proinflammatory mediators into the blood, but it remains unclear why these mediators induce inflammation especially in the lung. One of the first events occurring during the progression of acute pancreatitis is the induction of P-selectin expression in the endothelial cells of the lung. This expression has been associated with the generation of superoxide radicals by circulating xanthine oxidase. Because this enzyme needs molecular oxygen to perform the reaction, we have hypothesized that oxygen present in the alveolar space favors the generation of free radicals by xanthine oxidase and explains why P-selectin is expressed only in the lung. For this purpose, we evaluated the progression of the inflammatory process in rats with induced acute pancreatitis and one lung breathing nitrogen while the other lung continued breathing air. Acute pancreatitis was induced by intraductal administration of taurocholate and myeloperoxidase; P-selectin expression was measured 3 h after induction. Results indicated that, in the absence of oxygen in the alveolar space, the xanthine oxidase-dependent P-selectin expression did not occur and lung inflammation was significantly reduced.
Department of Experimental Pathology, Institut d'Investigacions Biomèdiques de Barcelona-Consejo Superior de Investigaciones Científicas, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain. dcabam@iibb.csic.es
Susana
S
Granell
Anna
A
Serrano-Mollar
Emma
E
Folch-Puy
Daniel
D
Navajas
Ramón
R
Farre
Oriol
O
Bulbena
Daniel
D
Closa
D000818:Animals; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008297:Male; D010100:Oxygen / Q000378:metabolism*; D019007:P-Selectin / Q000378:metabolism*; D010195:Pancreatitis / Q000139:chemically induced / Q000378:metabolism*; D009195:Peroxidase / Q000633:toxicity; D011650:Pulmonary Alveoli / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D013481:Superoxides / Q000378:metabolism; D013656:Taurocholic Acid / Q000633:toxicity; D014969:Xanthine Oxidase / Q000378:metabolism*
D019007:P-Selectin; D013481:Superoxides; D013656:Taurocholic Acid; D009195:Peroxidase; D014969:Xanthine Oxidase; D010100:Oxygen