Role of P-selectin and ICAM-1 in pancreatitis-induced lung inflammation in rats: significance of oxidative stress.
OBJECTIVE
To investigate the role of P-selectin and intercellular adhesion molecule-1 (ICAM-1) in the pathogenesis of lung injury associated with pancreatitis, and the relation between xanthine oxidase-derived oxidants and expression of these adhesion molecules.


BACKGROUND
In acute pancreatitis, acute respiratory distress syndrome occurs in the early stages of disease. This process is mediated by neutrophil infiltration.


METHODS
Pancreatitis was induced in rats by intraductal administration of 5% sodium taurocholate. ICAM-1 and P-selectin expression was measured using radiolabeled monoclonal antibodies. Neutrophil infiltration and plasma levels of xanthine oxidase were also evaluated.


RESULTS
Pancreatitis induces increases in P-selectin expression in lung, whereas ICAM-1 is unchanged from baseline levels. Immunoneutralization of either P-selectin or ICAM-1 prevents the infiltration of neutrophils into the lung. Xanthine and xanthine oxidase activity were increased after induction of pancreatitis. Xanthine oxidase inhibition prevents the upregulation of P-selectin in lung and neutrophil infiltration.


CONCLUSIONS
During acute pancreatitis, P-selectin is upregulated in the pulmonary endothelium and is a key determinant of leukocyte recruitment. Constitutive ICAM-1 is also involved in the process of cell infiltration into the lung. The increased expression of P-selectin appears to be triggered by a mechanism dependent on free radicals generated by xanthine oxidase released by the damaged pancreas.
Folch
E
E
Department of Medical Bioanalysis, Institut d'Investigacions Biomèdiques de Barcelona, Consejo Superior de Investigaciones Científicas, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.
Salas
A
A
Panés
J
J
Gelpí
E
E
Roselló-Catafau
J
J
Anderson
D C
DC
Navarro
S
S
Piqué
J M
JM
Fernández-Cruz
L
L
Closa
D
D
D000208:Acute Disease; D000818:Animals; D004195:Disease Models, Animal; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism / Q000502:physiology*; D008168:Lung / Q000201:enzymology; D008297:Male; D020556:Neutrophil Infiltration; D018384:Oxidative Stress; D019007:P-Selectin / Q000378:metabolism / Q000502:physiology*; D010195:Pancreatitis / Q000150:complications / Q000503:physiopathology*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012128:Respiratory Distress Syndrome / Q000209:etiology / Q000503:physiopathology*; D015854:Up-Regulation
D019007:P-Selectin; D018799:Intercellular Adhesion Molecule-1; D009195:Peroxidase