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. 1983 Nov;113(2):222–234.

Increased atherosclerosis and glomerulonephritis in cynomolgus monkeys (Macaca fascicularis) given injections of BSA over an extended period of time.

H F Stills Jr, B C Bullock, T B Clarkson
PMCID: PMC1916368  PMID: 6227252

Abstract

A study was conducted to compare the effects of experimental immune complex disease on the development of glomerulonephritis and aortic and coronary artery atherosclerosis. Fourteen adult male macaques (Macaca fascicularis) were fed a mildly atherogenic diet. Ten of these animals were given repeated intravenous injections of bovine serum albumin (BSA), and the remaining 4 were given similar injections of saline. Three of the monkeys given BSA responded with a high antibody titer, 4 with a moderate titer, and 3 with a low level titer to BSA. In all 4 monkeys with the moderate antibody response glomerulonephritis developed, characterized by increased glomerular cellularity, electron-dense deposits in the glomerular capillary basal lamina, and deposits of IgG, IgM, C3, C4, and BSA. Glomerulonephritis was not seen in the other 6 monkeys given BSA or the 4 control monkeys. Aortic lesions seen at necropsy consisted of a few fatty intimal streaks with no differences between test monkeys (given BSA) and control monkeys (given saline). There was no correlation between total serum cholesterol concentration, high-density lipoprotein cholesterol concentration, or BSA antibody levels and the degree of aortic atherosclerosis. Immunochemical stains for immunoglobulins and complement components revealed increased intimal staining when intimal thickness increased. Medial staining for immunoglobulin and complement components appeared to be slightly increased in monkeys with moderately high-level titers of BSA. The extent of atherosclerosis in the coronary arteries of monkeys given BSA was greater than in the control animals. Differences in the extent and severity of the atherosclerotic lesions were most pronounced in the proximal portions of the main coronary arteries, suggesting an increased susceptibility of this site to immune-complex-exacerbated atherosclerosis. In addition to the increased lesion severity in monkeys given BSA, there were numerous granulocytes seen within, attached to, and penetrating into the intima of the coronary lesions. No correlation was seen between the development of glomerulonephritis and either aortic or coronary artery atherosclerosis.

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Selected References

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  1. DIXON F. J., FELDMAN J. D., VAZQUEZ J. J. Experimental glomerulonephritis. The pathogenesis of a laboratory model resembling the spectrum of human glomerulonephritis. J Exp Med. 1961 May 1;113:899–920. doi: 10.1084/jem.113.5.899. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Dreesman G. R., Germuth F. G., Jr Immune complex disease. IV. The nature of the circulating complexes associated with glomerulonephritis in the acute BSA-rabbit system. Johns Hopkins Med J. 1972 Jun;130(6):335–343. [PubMed] [Google Scholar]
  3. FARR R. S. A quantitative immunochemical measure of the primary interaction between I BSA and antibody. J Infect Dis. 1958 Nov-Dec;103(3):239–262. doi: 10.1093/infdis/103.3.239. [DOI] [PubMed] [Google Scholar]
  4. Germuth F. G., Jr, Senterfit L. B., Dreesman G. R. Immune complex disease. V. The nature of the circulating complexes associated with glomerular alterations in the chronic BSA-rabbit system. Johns Hopkins Med J. 1972 Jun;130(6):344–357. [PubMed] [Google Scholar]
  5. Germuth F. G., Jr, Senterfit L. B., Pollack A. D. Immune complex disease. I. Experimental acute and chronic glomerulonephritis. Johns Hopkins Med J. 1967 Apr;120(4):225–251. [PubMed] [Google Scholar]
  6. Germuth F. G., Jr, Taylor J. J., Siddiqui S. Y., Rodriguez E. Immune complex disease. VI. Some determinants of the varieties of glomerular lesions in the chronic bovine serum albumin-rabbit system. Lab Invest. 1977 Aug;37(2):162–169. [PubMed] [Google Scholar]
  7. Hardin N. J., Minick C. R., Murphy G. E. Experimental induction of atheroarteriosclerosis by the synergy of allergic injury to arteries and lipid-rich diet. 3. The role of earlier acquired fibromuscular intimal thickening in the pathogenesis of later developing atherosclerosis. Am J Pathol. 1973 Nov;73(2):301–326. [PMC free article] [PubMed] [Google Scholar]
  8. Hollander W., Colombo M. A., Kirkpatrick B., Paddock J. Soluble proteins in the human atherosclerotic plaque. With spectral reference to immunoglobulins, C3-complement component, alpha 1-antitrypsin and alpha 2-macroglobulin. Atherosclerosis. 1979 Dec;34(4):391–405. doi: 10.1016/0021-9150(79)90064-9. [DOI] [PubMed] [Google Scholar]
  9. Hollander W., Colombo M. A., Kramsch D. M., Kirkpatrick B. Immunologial aspects of atherosclerosis. Adv Cardiol. 1974;13:192–207. doi: 10.1159/000395538. [DOI] [PubMed] [Google Scholar]
  10. Howard A. N., Patelski J., Bowyer D. E., Gresham G. A. Atherosclerosis induced in hypercholesterolaemic baboons by immunological injury; and the effects of intravenous polyunsaturated phosphatidyl choline. Atherosclerosis. 1971 Jul-Aug;14(1):17–29. doi: 10.1016/0021-9150(71)90035-9. [DOI] [PubMed] [Google Scholar]
  11. Lamberson H. V., Jr, Fritz K. E. Immunological enhancement of atherogenesis in rabbits. Persistent susceptibility to atherogenic diet following experimentally induced serum sickness. Arch Pathol. 1974 Jul;98(1):9–16. [PubMed] [Google Scholar]
  12. Minick C. R., Murphy G. E., Campbell W. G., Jr Experimental induction of athero-arteriosclerosis by the synergy of allergic injury to arteries and lipid-rich diet. I. Effect of repeated injections of horse serum in rabbits fed a dietary cholesterol supplement. J Exp Med. 1966 Oct 1;124(4):635–652. doi: 10.1084/jem.124.4.635. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Minick C. R., Murphy G. E. Experimental induction of atheroarteriosclerosis by the synergy of allergic injury to arteries and lipid-rich diet. II. Effect of repeatedly injected foreign protein in rabbits fed a lipid-rich, cholesterol-poor diet. Am J Pathol. 1973 Nov;73(2):265–300. [PMC free article] [PubMed] [Google Scholar]
  14. Sharma H. M., Geer J. C. Experimental aortic lesions of acute serum sickness in rabbits. Am J Pathol. 1977 Aug;88(2):255–266. [PMC free article] [PubMed] [Google Scholar]
  15. Valdes A. J., Senterfit L. B., Pollack A. D., Germuth F. G., Jr The effect of antigen excess on chronic immune complex glomerulonephritis. Johns Hopkins Med J. 1969 Jan;124(1):9–17. [PubMed] [Google Scholar]
  16. Van Winkle M., Levy L. Effect of removal of cholesterol diet upon serum sickness-cholesterol-induced atherosclerosis. J Exp Med. 1968 Sep 1;128(3):497–515. doi: 10.1084/jem.128.3.497. [DOI] [PMC free article] [PubMed] [Google Scholar]

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