H(2)O(2) and PARS mediate lung P-selectin upregulation in acute pancreatitis.
P-selectin and circulating xanthine oxidase are involved in the process of neutrophil infiltration into the lung associated with acute pancreatitis. This study investigated the mediators that trigger the upregulation of P-selectin in this process. Pancreatitis was induced in rats by intraductal administration of 5% sodium taurocholate. P-selectin expression was measured using radiolabeled antibodies. Neutrophil infiltration and PAF levels were also evaluated. The role of superoxide radical, H(2)O(2), or the enzyme poly (ADP-ribose) synthetase (PARS) on these processes was determined in groups of animals treated with the corresponding inhibitors. Pancreatitis was associated with an increase in P-selectin expression in the lung. Inhibition of PARS or H(2)O(2) abrogated P-selectin upregulation, PAF generation, and neutrophil recruitment. Superoxide dismutation prevented neutrophil recruitment and PAF generation, but had no effect on P-selectin expression. We conclude that during acute pancreatitis, upregulation of P-selectin in the pulmonary endothelium is triggered by H(2)O(2) and PARS activity.
Folch
E
E
Department of Medical Bioanalysis, IIBB-CSIC,IDIBAPS, Barcelona, Spain.
Salas
A
A
Prats
N
N
Panés
J
J
Piqué
J M
JM
Gelpí
E
E
Roselló-Catafau
J
J
Closa
D
D
D000208:Acute Disease; D000681:Amylases / Q000097:blood; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D002374:Catalase / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016166:Free Radical Scavengers; D005786:Gene Expression Regulation / Q000187:drug effects*; D006861:Hydrogen Peroxide / Q000378:metabolism*; D008049:Lipase / Q000097:blood; D008168:Lung / Q000378:metabolism*; D008297:Male; D019007:P-Selectin / Q000096:biosynthesis* / Q000235:genetics; D010195:Pancreatitis / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism; D010972:Platelet Activating Factor / Q000378:metabolism; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012128:Respiratory Distress Syndrome / Q000209:etiology / Q000378:metabolism; D013482:Superoxide Dismutase / Q000494:pharmacology; D013656:Taurocholic Acid / Q000633:toxicity; D014969:Xanthine Oxidase / Q000378:metabolism
D001549:Benzamides; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D019007:P-Selectin; D010972:Platelet Activating Factor; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D013656:Taurocholic Acid; C025160:3-aminobenzamide; D006861:Hydrogen Peroxide; D002374:Catalase; D009195:Peroxidase; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase; D011065:Poly(ADP-ribose) Polymerases; D008049:Lipase; D000681:Amylases