H(2)O(2) and PARS mediate lung P-selectin upregulation in acute pancreatitis

Free Radic Biol Med. 2000 Apr 15;28(8):1286-94. doi: 10.1016/s0891-5849(00)00245-8.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Amylases / blood
  • Animals
  • Benzamides / pharmacology
  • Catalase / pharmacology
  • Endothelium, Vascular / metabolism*
  • Enzyme Inhibitors / pharmacology
  • Free Radical Scavengers
  • Gene Expression Regulation / drug effects*
  • Hydrogen Peroxide / metabolism*
  • Lipase / blood
  • Lung / metabolism*
  • Male
  • P-Selectin / biosynthesis*
  • P-Selectin / genetics
  • Pancreatitis / complications
  • Pancreatitis / genetics
  • Pancreatitis / metabolism*
  • Peroxidase / metabolism
  • Platelet Activating Factor / metabolism
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Poly(ADP-ribose) Polymerases / physiology*
  • Rats
  • Rats, Wistar
  • Respiratory Distress Syndrome / etiology
  • Respiratory Distress Syndrome / metabolism
  • Superoxide Dismutase / pharmacology
  • Taurocholic Acid / toxicity
  • Xanthine Oxidase / metabolism

Substances

  • Benzamides
  • Enzyme Inhibitors
  • Free Radical Scavengers
  • P-Selectin
  • Platelet Activating Factor
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Taurocholic Acid
  • 3-aminobenzamide
  • Hydrogen Peroxide
  • Catalase
  • Peroxidase
  • Superoxide Dismutase
  • Xanthine Oxidase
  • Poly(ADP-ribose) Polymerases
  • Lipase
  • Amylases