Neutrophils accentuate ischemia-reperfusion injury in isolated perfused rat kidneys.
The contribution of neutrophils to reperfusion injury after ischemia is not known. To determine the effect of neutrophils on the function of ischemic kidneys, we added purified human neutrophils during perfusion of isolated ischemic or nonischemic rat kidneys. Reperfusion of ischemic kidneys with neutrophils caused a distinct morphological lesion of vascular endothelial and smooth muscle cells and more functional injury than reperfusion with buffered albumin alone; with neutrophils, glomerular filtration rate (GFR) was 113 +/- 7 microliter.min-1.g-1, tubular sodium reabsorption (TNa) was 72 +/- 2%; without neutrophils, GFR was 222 +/- 18 microliter.min-1.g-1; TNa was 90 +/- 2%; both P less than 0.01 vs. reperfusion with neutrophils. In contrast, addition of neutrophils did not injure control kidneys, unless the neutrophil activator, phorbol myristate acetate, was also added. Two experiments suggested that O2 metabolites contributed to neutrophil-mediated injury to ischemic kidneys. First, reperfusion of ischemic kidneys with O2 metabolite-deficient neutrophils from a patient with chronic granulomatous disease did not cause more injury than reperfusion with buffered albumin alone. Second, simultaneous addition of the O2 metabolite scavenger, catalase, prevented the GFR and TNa decreases caused by neutrophils but did not decrease injury in the absence of neutrophils. We conclude that neutrophils by an O2 metabolite-dependent mechanism contribute to ischemia-reperfusion injury in the isolated perfused kidney.
Linas
S L
SL
Department of Medicine, University of Colorado, Denver.
Shanley
P F
PF
Whittenburg
D
D
Berger
E
E
Repine
J E
JE
D000818:Animals; D001158:Arteries / Q000473:pathology / Q000503:physiopathology; D002448:Cell Adhesion; D006861:Hydrogen Peroxide / Q000097:blood; D007511:Ischemia / Q000473:pathology / Q000503:physiopathology*; D007668:Kidney / Q000098:blood supply* / Q000503:physiopathology; D008297:Male; D009504:Neutrophils / Q000166:cytology / Q000502:physiology*; D009928:Organ Specificity; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D012039:Regional Blood Flow; D013481:Superoxides / Q000097:blood
D013481:Superoxides; D006861:Hydrogen Peroxide