Role of P-selectin and ICAM-1 in pancreatitis-induced lung inflammation inrats - 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 panc reatitis, and the relation between xanthine oxidase-derived oxidants and ex pression of these adhesion molecules. Summary Background Data In acute pancreatitis, acute respiratory distress s yndrome 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 leve ls of xanthine oxidase were also evaluated. Results Pancreatitis induces increases in P-selectin expression in lung, wh ereas ICAM-1 is unchanged from baseline levels. Immunoneutralization of eit her 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 pul monary endothelium and is a key determinant of leukocyte recruitment. Const itutive ICAM-1 is also involved in the process of cell infiltration into th e lung. The increased expression of P-selectin appears to be triggered by a mechanism dependent on free radicals generated by xanthine oxidase release d by the damaged pancreas.