Abstract
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.
Full text
PDFSelected References
These references are in PubMed. This may not be the complete list of references from this article.
- Beatty P. G., Ledbetter J. A., Martin P. J., Price T. H., Hansen J. A. Definition of a common leukocyte cell-surface antigen (Lp95-150) associated with diverse cell-mediated immune functions. J Immunol. 1983 Dec;131(6):2913–2918. [PubMed] [Google Scholar]
- Bird J. E., Milhoan K., Wilson C. B., Young S. G., Mundy C. A., Parthasarathy S., Blantz R. C. Ischemic acute renal failure and antioxidant therapy in the rat. The relation between glomerular and tubular dysfunction. J Clin Invest. 1988 May;81(5):1630–1638. doi: 10.1172/JCI113498. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brezis M., Shanley P., Silva P., Spokes K., Lear S., Epstein F. H., Rosen S. Disparate mechanisms for hypoxic cell injury in different nephron segments. Studies in the isolated perfused rat kidney. J Clin Invest. 1985 Nov;76(5):1796–1806. doi: 10.1172/JCI112171. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Campbell E. J., Senior R. M., McDonald J. A., Cox D. L. Proteolysis by neutrophils. Relative importance of cell-substrate contact and oxidative inactivation of proteinase inhibitors in vitro. J Clin Invest. 1982 Oct;70(4):845–852. doi: 10.1172/JCI110681. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cross C. E., Halliwell B., Borish E. T., Pryor W. A., Ames B. N., Saul R. L., McCord J. M., Harman D. Oxygen radicals and human disease. Ann Intern Med. 1987 Oct;107(4):526–545. doi: 10.7326/0003-4819-107-4-526. [DOI] [PubMed] [Google Scholar]
- Flores J., DiBona D. R., Beck C. H., Leaf A. The role of cell swelling in ischemic renal damage and the protective effect of hypertonic solute. J Clin Invest. 1972 Jan;51(1):118–126. doi: 10.1172/JCI106781. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gamelin L. M., Zager R. A. Evidence against oxidant injury as a critical mediator of postischemic acute renal failure. Am J Physiol. 1988 Sep;255(3 Pt 2):F450–F460. doi: 10.1152/ajprenal.1988.255.3.F450. [DOI] [PubMed] [Google Scholar]
- Granger D. N., McCord J. M., Parks D. A., Hollwarth M. E. Xanthine oxidase inhibitors attenuate ischemia-induced vascular permeability changes in the cat intestine. Gastroenterology. 1986 Jan;90(1):80–84. doi: 10.1016/0016-5085(86)90078-8. [DOI] [PubMed] [Google Scholar]
- Harlan J. M. Neutrophil-mediated vascular injury. Acta Med Scand Suppl. 1987;715:123–129. doi: 10.1111/j.0954-6820.1987.tb09912.x. [DOI] [PubMed] [Google Scholar]
- Hellberg P. O., Källskog O., Wolgast M., Ojteg G. Effects of neutrophil granulocytes on the inulin barrier of renal tubular epithelium after ischaemic damage. Acta Physiol Scand. 1988 Oct;134(2):313–315. doi: 10.1111/j.1748-1716.1988.tb08496.x. [DOI] [PubMed] [Google Scholar]
- Hernandez L. A., Grisham M. B., Twohig B., Arfors K. E., Harlan J. M., Granger D. N. Role of neutrophils in ischemia-reperfusion-induced microvascular injury. Am J Physiol. 1987 Sep;253(3 Pt 2):H699–H703. doi: 10.1152/ajpheart.1987.253.3.H699. [DOI] [PubMed] [Google Scholar]
- Johnson R. J., Klebanoff S. J., Ochi R. F., Adler S., Baker P., Sparks L., Couser W. G. Participation of the myeloperoxidase-H2O2-halide system in immune complex nephritis. Kidney Int. 1987 Sep;32(3):342–349. doi: 10.1038/ki.1987.215. [DOI] [PubMed] [Google Scholar]
- Klausner J. M., Paterson I. S., Goldman G., Kobzik L., Rodzen C., Lawrence R., Valeri C. R., Shepro D., Hechtman H. B. Postischemic renal injury is mediated by neutrophils and leukotrienes. Am J Physiol. 1989 May;256(5 Pt 2):F794–F802. doi: 10.1152/ajprenal.1989.256.5.F794. [DOI] [PubMed] [Google Scholar]
- Linas S. L., Shanley P. F., Whittenburg D., Berger E., Repine J. E. Neutrophils accentuate ischemia-reperfusion injury in isolated perfused rat kidneys. Am J Physiol. 1988 Oct;255(4 Pt 2):F728–F735. doi: 10.1152/ajprenal.1988.255.4.F728. [DOI] [PubMed] [Google Scholar]
- Manson P. N., Anthenelli R. M., Im M. J., Bulkley G. B., Hoopes J. E. The role of oxygen-free radicals in ischemic tissue injury in island skin flaps. Ann Surg. 1983 Jul;198(1):87–90. doi: 10.1097/00000658-198307000-00017. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nordström G., Seeman T., Hasselgren P. O. Beneficial effect of allopurinol in liver ischemia. Surgery. 1985 Jun;97(6):679–684. [PubMed] [Google Scholar]
- Paller M. S. Effect of neutrophil depletion on ischemic renal injury in the rat. J Lab Clin Med. 1989 Mar;113(3):379–386. [PubMed] [Google Scholar]
- Paller M. S., Hoidal J. R., Ferris T. F. Oxygen free radicals in ischemic acute renal failure in the rat. J Clin Invest. 1984 Oct;74(4):1156–1164. doi: 10.1172/JCI111524. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schmid-Schönbein G. W. Capillary plugging by granulocytes and the no-reflow phenomenon in the microcirculation. Fed Proc. 1987 May 15;46(7):2397–2401. [PubMed] [Google Scholar]
- Stewart J. R., Blackwell W. H., Crute S. L., Loughlin V., Greenfield L. J., Hess M. L. Inhibition of surgically induced ischemia/reperfusion injury by oxygen free radical scavengers. J Thorac Cardiovasc Surg. 1983 Aug;86(2):262–272. [PubMed] [Google Scholar]
- Vedder N. B., Winn R. K., Rice C. L., Chi E. Y., Arfors K. E., Harlan J. M. A monoclonal antibody to the adherence-promoting leukocyte glycoprotein, CD18, reduces organ injury and improves survival from hemorrhagic shock and resuscitation in rabbits. J Clin Invest. 1988 Mar;81(3):939–944. doi: 10.1172/JCI113407. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zager R. A., Mahan J., Merola A. J. Effects of mannitol on the postischemic kidney. Biochemical, functional, and morphologic assessments. Lab Invest. 1985 Oct;53(4):433–442. [PubMed] [Google Scholar]