Effect of neutrophil depletion on ischemic renal injury in the rat.
Oxygen free radicals have been implicated in postischemic renal injury. However, the source of these oxygen free radicals has not been well defined. One potential source is activated neutrophils. Neutrophil depletion was produced in rats by using two different techniques, and the effect on ischemic injury was examined. Rabbit anti-rat neutrophil serum was prepared by immunizing a rabbit with a Percoll gradient centrifugation-purified (approximately 90%) suspension of rat neutrophils. Rats received antineutrophil serum in one of four protocols and were subsequently subjected to 40 minutes of renal artery occlusion. Control animals received nonimmune rabbit serum. The serum creatinine levels 24 hours after ischemia were not different between control and immune serum-treated rats in any of the protocols despite significant reductions in absolute neutrophil count. In a separate study, nitrogen mustard was administered 40 hours before ischemia. Nitrogen mustard-treated rats developed moderate neutropenia and 24 hours after ischemia had lower serum creatinine levels and higher inulin clearance. However, nitrogen mustard-treated rats lost 31.5 +/- 5 gm body weight in the 2 days after nitrogen mustard administration, whereas control animals gained 5.9 +/- 5.9 gm during the same interval. Furthermore, among nitrogen mustard-treated rats there was no correlation between neutrophil count and postischemic renal function. It is thus possible that the beneficial effects of nitrogen mustard were caused by a mechanism other than neutrophil depletion. In summary, in four protocols that used antineutrophil serum, neutropenia did not protect against ischemic injury. Nitrogen mustard provided protection, but probably by a neutrophil-independent mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)
Paller
M S
MS
Department of Medicine, University of Minnesota, Minneapolis 55455.
D000818:Animals; D005609:Free Radicals; D007511:Ischemia / Q000473:pathology / Q000503:physiopathology*; D007668:Kidney / Q000098:blood supply* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009503:Neutropenia / Q000503:physiopathology; D009504:Neutrophils / Q000502:physiology*; D009588:Nitrogen Mustard Compounds / Q000494:pharmacology; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D005609:Free Radicals; D009588:Nitrogen Mustard Compounds; D010100:Oxygen