Medical College of Wisconsin
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Neutrophil-dependent, oxygen-radical mediated lung injury associated with acute pancreatitis. Ann Surg 1989 Dec;210(6):740-7

Date

12/01/1989

Pubmed ID

2589887

Pubmed Central ID

PMC1357865

DOI

10.1097/00000658-198912000-00008

Scopus ID

2-s2.0-0024811721 (requires institutional sign-in at Scopus site)   154 Citations

Abstract

Cerulein-induced acute pancreatitis in rats is associated with a reversible lung injury that is characterized by alveolar capillary endothelial-cell injury, increased microvascular permeability, interstitial edema formation, and intraalveolar hemorrhage and fibrin deposition. The role of mediators in this injury was analyzed using gravimetric data, microvascular permeability indices, electron microscopy, and a quantitative morphometric analysis. Neutrophil depletion induced by a specific antibody was highly protective against lung injury. Interruption of the complement pathway (using low dose Naja naja cobra venom factor) also protected against lung injury. Catalase and superoxide dismutase were also protective. The iron chelator deferoxamine and the hydroxyl radical scavenger, dimethylsulfoxide, were not protective against acute lung injury. These data suggest that complement, neutrophils, and neutrophil-derived (H2O2-dependent) oxygen products mediate lung injury that occurs secondary to cerulein-induced pancreatitis. In contrast to other models of neutrophil-dependent, oxygen-radical-mediated lung injury, this lung injury does not appear to be an iron-dependent and hydroxyl-radical mediated injury. We postulate that the process of acute pancreatitis leads to complement activation followed by neutrophil recruitment, sequestration, and adherence to alveolar capillary endothelial cells. Ultimately lung injury appears to result from local endothelial-cell injury secondary to neutrophil-generated oxygen products that may be myeloperoxidase dependent.

Author List

Guice KS, Oldham KT, Caty MG, Johnson KJ, Ward PA



MESH terms used to index this publication - Major topics in bold

Acute Disease
Animals
Capillary Permeability
Ceruletide
Complement System Proteins
Drug Combinations
Endothelium, Vascular
Free Radicals
Hydrogen Peroxide
Lung Diseases
Male
Neutropenia
Neutrophils
Oxygen
Pancreatitis
Polyethylene Glycols
Pulmonary Alveoli
Rats
Superoxide Dismutase