An evaluation of the neutrophil as a mediator of in vivo renal ischemic-reperfusion injury.
Previous studies indicated that administration of a monoclonal antibody (MoAb 60.3), which blocks neutrophil adherence to rabbit endothelial cells, prevents ischemic-reperfusion (I-R) injury in multiple extrarenal organs. These findings indicated that the neutrophil can be a critical mediator of I-R tissue damage. To assess whether the neutrophil affects renal I-R injury, MoAb 60.3 was given to rabbits that were then subjected to either 50 minutes or 38 minutes of renal ischemia induced by renal artery occlusion (RAO). The severity of kidney damage was assessed 24 and 48 hours later by blood urea nitrogen and plasma creatinine concentrations and by renal histology. The results were compared with those obtained in time-matched RAO controls. MoAb 60.3 conferred no functional or morphologic protection against either severe or mild ischemic insults. To further evaluate whether neutrophils affect renal I-R injury, rats were depleted of neutrophils (less than 200 cells/mm3) by anti-neutrophil serum administration and then they were subjected to either 37 minutes or 29 minutes of RAO. Neutrophil depletion conferred neither functional nor morphologic protection when compared with time-matched RAO controls. It was concluded that the uniform lack of protection noted in these experiments, despite that two different animals, two different ways of interfering with neutrophil function, and differing severities of ischemic injury were studied, strongly suggests that the neutrophil is not a critical participant in the renal I-R injury process.
Department of Medicine, University of Washington, Seattle.
M A
MA
Thornton
R
R
Winn
C E
CE
Alpers
R A
RA
Zager
D058186:Acute Kidney Injury / Q000097:blood / Q000473:pathology; D000818:Animals; D000911:Antibodies, Monoclonal; D005260:Female; D007668:Kidney / Q000473:pathology*; D009504:Neutrophils / Q000502:physiology*; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D015427:Reperfusion Injury / Q000097:blood / Q000473:pathology*
D000911:Antibodies, Monoclonal