Neutrophil-dependent, oxygen-radical mediated lung injury associated with acute pancreatitis.
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.
Guice
K S
KS
Section of General Surgery, University of Michigan Medical School, Ann Arbor.
Oldham
K T
KT
Caty
M G
MG
Johnson
K J
KJ
Ward
P A
PA
D000208:Acute Disease; D000818:Animals; D002199:Capillary Permeability; D002108:Ceruletide; D003165:Complement System Proteins; D004338:Drug Combinations; D004730:Endothelium, Vascular; D005609:Free Radicals; D006861:Hydrogen Peroxide; D008171:Lung Diseases / Q000209:etiology* / Q000503:physiopathology; D008297:Male; D009503:Neutropenia / Q000150:complications; D009504:Neutrophils; D010100:Oxygen; D010195:Pancreatitis / Q000139:chemically induced / Q000150:complications* / Q000503:physiopathology; D011092:Polyethylene Glycols; D011650:Pulmonary Alveoli / Q000503:physiopathology; D051381:Rats; D013482:Superoxide Dismutase / Q000502:physiology
D004338:Drug Combinations; D005609:Free Radicals; D011092:Polyethylene Glycols; D002108:Ceruletide; D003165:Complement System Proteins; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase; D010100:Oxygen