Original article| Volume 113, ISSUE 3, P379-386, March 1989

Effect of neutrophil depletion on ischemic renal injury in the rat

  • Mark S. Paller
    Reprint requests: Mark S. Paller, MD, University of Minnesota, Box 736 UMHC, Minneapolis, MN 55455.
    From the Department of Medicine, University of Minnesota Minneapolis, Minnesota U.S.A.
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      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 neutrophll-independent mechanism. We conclude that there is no clear-cut role of circulating neutrophils to mediate ischemic renal injury in the rat.
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        • McCord JM
        Oxygen-derived free radicals in postischemic tissue injury.
        N Engl J Med. 1985; 312: 159-163
        • Paller MS
        • Hoidal JR
        • Ferris TF
        Oxygen free radicals in ischemic acute renal failure in the rat.
        J Clin Invest. 1984; 74: 1156-1164
        • Paller MS
        • Hebbel RP
        Ethane production as a measure of lipid peroxidation after renal ischemia.
        Am J Physiol. 1986; 251: F839-F843
        • Hansson R
        • Jonsson O
        • Lundstam S
        • Petterson S
        • Schersten T
        • Waldenstrom J
        Effects of free radical scavengers on renal circulation after ischemia in the rabbit.
        Clin Sci. 1983; 65: 605-610
        • Baker GL
        • Corry RJ
        • Autor AP
        Oxygen free radical induced damage in kidneys subjected to warm ischemia and reperfusion: protective effect of superoxide dismutase.
        Ann Surg. 1985; 202: 628-641
        • Turrens JF
        • Boveris A
        Generation of superoxide anion by the NADH dehydrogenase of bovine heart mitochondria.
        Biochem J. 1980; 191: 421-427
        • Babior BM
        Oxygen-dependent microlinal killing by phagocytes.
        N Engl J Med. 1978; 298: 659-668
        • Babior BM
        Oxygen-dependent microlinal killing by phagocytes.
        N Engl J Med. 1978; 298: 721-725
        • Egan RW
        • Paxton J
        • Kuehl FA
        Mechanism for the irreversible self-deactivation of prostaglandin synthetase.
        J Biol Chem. 1976; 251: 7329-7335
        • Freeman BA
        Biological sites and mechanisms of free radical production.
        Aging. 1984; 27: 43-52
        • Romson JL
        • Hook BG
        • Kunkel SL
        • Abrams GD
        • Schork MA
        • Lucchesi BR
        Reduction of the extent of ischemic myocardial injury by neutrophil depletion in the dog.
        Circulation. 1983; 67: 1016-1023
        • Mullane KM
        • Read N
        • Salmon JA
        • Moncada S
        Role of leukocytes in acute myocardial infarction in anesthetized dogs: relationship to myocardial salvage by anti-inflammatory drugs.
        J Pharmacol Exp Ther. 1984; 228: 510-522
        • Engler RL
        • Dahlgren MD
        • Morris DD
        • Peterson MA
        • Schmid-Schonbein GW
        Role of leukocytes in response to acute myocardial ischemia and reflow in dogs.
        Am J Physiol. 1986; 251: H314-H322
        • Engler R
        • Covell JW
        Granulocytes cause reperfusion ventricular dysfunction after 15-minute ischemia in the dog.
        Circ Res. 1987; 61: 20-28
        • Grisham MB
        • Hernandez LA
        • Granger DN
        Xanthine oxidase and neutrophil infiltration in intestinal ischemia.
        Am J Physiol. 1986; 251: G567-G574
        • Solez K
        • Kramer EC
        • Fox JA
        • Heptinstall RH
        Medullary plasma flow and intravascular leukocyte accumulation in acute renal failure.
        Kidney Int. 1974; 6: 24-37
        • Solez K
        The pathology and pathogenesis of human “acute tubular necrosis”.
        in: Solez K Whetton A Acute renal failure. Correlations between morphology and function. Marcel Dekker, New York1984: 17
        • Linas SL
        • Whittenburg D
        • Berger E
        • Repine JE
        Neutrophils accentuate renal ischemia-reperfusion injury in the isolated perfused rat kidneys.
        Am J Physiol. 1988; 255: F728-F735
        • Watt SM
        • Burgess AW
        • Metcalf D
        Isolation and surface labeling of murine polymorphonuclear neutrophils.
        J Cell Physiol. 1979; 100: 1-22
        • Salant DJ
        • Belok S
        • Madaio MP
        • Couser WG
        A new role for complement in experimental membranous nephropathy in rats.
        J Clin Invest. 1980; 66: 1339-1350
        • Yam LT
        • Li CY
        • Crosby WH
        Cytochemical identification of monocytes and granulocytes.
        Am J Clin Pathol. 1971; 55: 283-290
        • Simon D
        • Luke RG
        Polymorphonuclear leucocytosis and lymphopenia in acute renal failure and metabolic acidosis in the rat.
        Clin Sci Mol Med. 1973; 45: 397-402
        • Andrews PM
        • Bates SB
        Dietary protein prior to renal ischemia dramatically affects postischemic kidney function.
        Kidney Int. 1986; 30: 299-303
        • Moorhouse PC
        • Grootveld M
        • Halliwell B
        • Quinlan JG
        • Gutteridge JMC
        Allopurinol and oxypurinol are hydroxyl radical scavengers.
        FEBS Lett. 1987; 213: 23-28
        • Paller MS
        • Hedlund BE
        Role of iron in postischemic renal injury in the rat.
        Kidney Int. 1988; 34: 474-480
        • Chambers DE
        • Parks DA
        • Patterson G
        • et al.
        Xanthine oxidase as a source of free radical damage in myocardial ischemia.
        J Mol Cell Cardiol. 1985; 17: 145-152
        • Brown JM
        • Terada LS
        • Grosso MA
        • et al.
        Xanthine oxidase produces hydrogen peroxide which contributes to reperfusion injury of ischemic, isolated, perfused rat hearts.
        J Clin Invest. 1988; 81: 1297-1301
        • Kehrer JP
        • Piper HM
        • Sies H
        Xanthine oxidase is not responsible for reoxygenation injury in isolated-perfused rat heart.
        Free Radic Res Commun. 1987; 3: 69-78