Mediators of ischemia-reperfusion injury of rat lung.
In rats, we characterized the mediators of lung reperfusion injury after ischemia. Animals underwent left lung ischemia. After 90 minutes of ischemia, reperfusion for up to 4 hours was evaluated. Lung injury, as determined by vascular leakage of serum albumin, increased in ischemic-reperfused animals when compared with time-matched sham controls. Injury was biphasic, peaking at 30 minutes and 4 hours of reperfusion. The late but not the early phase of reperfusion injury is known to be neutrophil dependent. Bronchoalveolar lavage of ischemic-reperfused lungs at 30 minutes and 4 hours of reperfusion demonstrated increased presence of serum albumin, indicative of damage to the normal vascular/airway barrier. Lung mRNA for rat monocyte chemoattractant protein-1 and tumor necrosis factor-alpha peaked very early (between 0.5 and 1.0 hour) during the reperfusion process. Development of injury was associated with a decline in serum complement activity and progressive intrapulmonary sequestration of neutrophils. Administration of superoxide dismutase before reperfusion resulted in reduction of injury at 30 minutes of reperfusion. Complement depletion decreased injury at both 30 minutes and 4 hours of reperfusion. Requirements for tumor necrosis factor-alpha, interferon-gamma, and monocyte chemoattractant protein-1 for early injury were shown whereas only tumor necrosis factor-alpha was involved at 4 hours. We propose that acute (30-minute) lung injury is determined in large part by products of activated lung macrophages whereas the delayed (4-hour) injury is mediated by products of activated and recruited neutrophils.
Eppinger
M J
MJ
Section of Thoracic Surgery, University of Michigan Medical Center, Ann Arbor, USA.
Deeb
G M
GM
Bolling
S F
SF
Ward
P A
PA
D000818:Animals; D015152:Blotting, Northern; D003167:Complement Activation; D003165:Complement System Proteins / Q000502:physiology; D016207:Cytokines / Q000502:physiology; D008168:Lung / Q000201:enzymology / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D012313:RNA / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D015427:Reperfusion Injury / Q000201:enzymology / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D013482:Superoxide Dismutase / Q000494:pharmacology
D016207:Cytokines; D012313:RNA; D003165:Complement System Proteins; D009195:Peroxidase; D013482:Superoxide Dismutase