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. 1993 Sep;143(3):814–822.

Effects of human immunodeficiency virus sera and macrophage supernatants on mesangial cell proliferation and matrix synthesis.

J Mattana 1, M Abramovici 1, P C Singhal 1
PMCID: PMC1887203  PMID: 8362979

Abstract

Patients with human immunodeficiency virus (HIV) infection are prone to the development of focal segmental glomerulosclerosis, a lesion in which increased mesangial cell proliferation and matrix synthesis may play a role. We undertook the present study to determine whether HIV sera may affect mesangial cell proliferation and matrix synthesis either directly or indirectly via effects on macrophage supernatants. Pooled HIV sera was found to significantly enhance (P < 0.01) mesangial cell proliferation in a concentration-related manner. Mesangial cell proliferation was significantly suppressed by two medications commonly utilized in HIV-infected patients, azidothymidine and trimethoprim/sulfamethoxazole, and was not significantly altered by lipopolysaccharide, suggesting that these medications as well as recurrent infection are unlikely to account for the proliferative effect of HIV sera. Supernatants from HIV sera-treated macrophages were found to significantly enhance (P < 0.01) mesangial cell incorporation of [3H]proline, a marker for synthesis of the matrix component collagen, compared to supernatants from control sera-treated macrophages. These results suggest that HIV sera may directly enhance mesangial cell proliferation and may indirectly increase mesangial cell matrix synthesis by altering macrophage secretory products. These effects may play a role in the development of glomerulosclerosis in patients with HIV infection.

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Selected References

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  1. Alpers C. E., McClure J., Bursten S. L. Human mesangial cells are resistant to productive infection by multiple strains of human immunodeficiency virus types 1 and 2. Am J Kidney Dis. 1992 Feb;19(2):126–130. doi: 10.1016/s0272-6386(12)70120-8. [DOI] [PubMed] [Google Scholar]
  2. Bourgoignie J. J., Meneses R., Ortiz C., Jaffe D., Pardo V. The clinical spectrum of renal disease associated with human immunodeficiency virus. Am J Kidney Dis. 1988 Aug;12(2):131–137. doi: 10.1016/s0272-6386(88)80008-8. [DOI] [PubMed] [Google Scholar]
  3. Bourgoignie J. J. Renal complications of human immunodeficiency virus type 1. Kidney Int. 1990 Jun;37(6):1571–1584. doi: 10.1038/ki.1990.151. [DOI] [PubMed] [Google Scholar]
  4. Boyce N. W., Tipping P. G., Holdsworth S. R. Glomerular macrophages produce reactive oxygen species in experimental glomerulonephritis. Kidney Int. 1989 Mar;35(3):778–782. doi: 10.1038/ki.1989.52. [DOI] [PubMed] [Google Scholar]
  5. Cohen A. H., Sun N. C., Shapshak P., Imagawa D. T. Demonstration of human immunodeficiency virus in renal epithelium in HIV-associated nephropathy. Mod Pathol. 1989 Mar;2(2):125–128. [PubMed] [Google Scholar]
  6. Cunningham E. E., Brentjens J. R., Zielezny M. A., Andres G. A., Venuto R. C. Heroin nephropathy. A clinicopathologic and epidemiologic study. Am J Med. 1980 Jan;68(1):47–53. doi: 10.1016/0002-9343(80)90164-3. [DOI] [PubMed] [Google Scholar]
  7. Cunningham E. E., Zielezny M. A., Venuto R. C. Heroin-associated nephropathy. A nationwide problem. JAMA. 1983 Dec 2;250(21):2935–2936. [PubMed] [Google Scholar]
  8. D'Agati V., Suh J. I., Carbone L., Cheng J. T., Appel G. Pathology of HIV-associated nephropathy: a detailed morphologic and comparative study. Kidney Int. 1989 Jun;35(6):1358–1370. doi: 10.1038/ki.1989.135. [DOI] [PubMed] [Google Scholar]
  9. Di Rienzo A. M., Petronini P. G., Guetard D., Favilla R., Borghetti A. F., Montagnier L., Piedimonte G. Modulation of cell growth and host protein synthesis during HIV infection in vitro. J Acquir Immune Defic Syndr. 1992;5(9):921–929. [PubMed] [Google Scholar]
  10. Ferrario F., Castiglione A., Colasanti G., Barbiano di Belgioioso G., Bertoli S., D'Amico G. The detection of monocytes in human glomerulonephritis. Kidney Int. 1985 Sep;28(3):513–519. doi: 10.1038/ki.1985.158. [DOI] [PubMed] [Google Scholar]
  11. Fine L. The biology of renal hypertrophy. Kidney Int. 1986 Mar;29(3):619–634. doi: 10.1038/ki.1986.45. [DOI] [PubMed] [Google Scholar]
  12. Floege J., Alpers C. E., Burns M. W., Pritzl P., Gordon K., Couser W. G., Johnson R. J. Glomerular cells, extracellular matrix accumulation, and the development of glomerulosclerosis in the remnant kidney model. Lab Invest. 1992 Apr;66(4):485–497. [PubMed] [Google Scholar]
  13. Floege J., Burns M. W., Alpers C. E., Yoshimura A., Pritzl P., Gordon K., Seifert R. A., Bowen-Pope D. F., Couser W. G., Johnson R. J. Glomerular cell proliferation and PDGF expression precede glomerulosclerosis in the remnant kidney model. Kidney Int. 1992 Feb;41(2):297–309. doi: 10.1038/ki.1992.42. [DOI] [PubMed] [Google Scholar]
  14. Fogo A., Hawkins E. P., Berry P. L., Glick A. D., Chiang M. L., MacDonell R. C., Jr, Ichikawa I. Glomerular hypertrophy in minimal change disease predicts subsequent progression to focal glomerular sclerosis. Kidney Int. 1990 Jul;38(1):115–123. doi: 10.1038/ki.1990.175. [DOI] [PubMed] [Google Scholar]
  15. Fogo A., Ichikawa I. Evidence for the central role of glomerular growth promoters in the development of sclerosis. Semin Nephrol. 1989 Dec;9(4):329–342. [PubMed] [Google Scholar]
  16. Green D. F., Resnick L., Bourgoignie J. J. HIV infects glomerular endothelial and mesangial but not epithelial cells in vitro. Kidney Int. 1992 Apr;41(4):956–960. doi: 10.1038/ki.1992.146. [DOI] [PubMed] [Google Scholar]
  17. Green S. J., Chen T. Y., Crawford R. M., Nacy C. A., Morrison D. C., Meltzer M. S. Cytotoxic activity and production of toxic nitrogen oxides by macrophages treated with IFN-gamma and monoclonal antibodies against the 73-kDa lipopolysaccharide receptor. J Immunol. 1992 Sep 15;149(6):2069–2075. [PubMed] [Google Scholar]
  18. Harris K. P., Lefkowith J. B., Klahr S., Schreiner G. F. Essential fatty acid deficiency ameliorates acute renal dysfunction in the rat after the administration of the aminonucleoside of puromycin. J Clin Invest. 1990 Oct;86(4):1115–1123. doi: 10.1172/JCI114816. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Holdsworth S. R., Neale T. J., Wilson C. B. Abrogation of macrophage-dependent injury in experimental glomerulonephritis in the rabbit. Use of an antimacrophage serum. J Clin Invest. 1981 Sep;68(3):686–698. doi: 10.1172/JCI110304. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Karlsson-Parra A., Dimény E., Fellström B., Klareskog L. HIV receptors (CD4 antigen) in normal human glomerular cells. N Engl J Med. 1989 Mar 16;320(11):741–741. doi: 10.1056/NEJM198903163201119. [DOI] [PubMed] [Google Scholar]
  21. Klahr S., Schreiner G., Ichikawa I. The progression of renal disease. N Engl J Med. 1988 Jun 23;318(25):1657–1666. doi: 10.1056/NEJM198806233182505. [DOI] [PubMed] [Google Scholar]
  22. Latta H., Fligiel S. Mesangial fenestrations, sieving, filtration, and flow. Lab Invest. 1985 Jun;52(6):591–598. [PubMed] [Google Scholar]
  23. Lovett D. H., Ryan J. L., Sterzel R. B. Stimulation of rat mesangial cell proliferation by macrophage interleukin 1. J Immunol. 1983 Dec;131(6):2830–2836. [PubMed] [Google Scholar]
  24. Markovic-Lipkovski J., Müller C. A., Risler T., Bohle A., Müller G. A. Mononuclear leukocytes, expression of HLA class II antigens and intercellular adhesion molecule 1 in focal segmental glomerulosclerosis. Nephron. 1991;59(2):286–293. doi: 10.1159/000186566. [DOI] [PubMed] [Google Scholar]
  25. Mattana J., Singhal P. C. Effects of prostaglandin E2 and cyclic AMP on uptake of immunoglobulin G complexes by cultured macrophages. Eicosanoids. 1992;5(2):67–72. [PubMed] [Google Scholar]
  26. Mattana J., Singhal P. C. Macrophage supernatants have both stimulatory and suppressive effects on mesangial cell proliferation. J Cell Physiol. 1993 Feb;154(2):289–293. doi: 10.1002/jcp.1041540211. [DOI] [PubMed] [Google Scholar]
  27. Monga G., Mazzucco G., di Belgiojoso G. B., Busnach G. Monocyte infiltration and glomerular hypercellularity in human acute and persistent glomerulonephritis. Light and electron microscopic, immunofluorescence, and histochemical investigation on twenty-eight cases. Lab Invest. 1981 Apr;44(4):381–387. [PubMed] [Google Scholar]
  28. Monga G., Mazzucco G., di Belgiojoso G. B., Busnach G. The presence and possible role of monocyte infiltration in human chronic proliferative glomerulonephritides. Light microscopic, immunofluorescence, and histochemical correlations. Am J Pathol. 1979 Feb;94(2):271–284. [PMC free article] [PubMed] [Google Scholar]
  29. Nathan C. F., Murray H. W., Cohn Z. A. The macrophage as an effector cell. N Engl J Med. 1980 Sep 11;303(11):622–626. doi: 10.1056/NEJM198009113031106. [DOI] [PubMed] [Google Scholar]
  30. Nathan C. F. Secretory products of macrophages. J Clin Invest. 1987 Feb;79(2):319–326. doi: 10.1172/JCI112815. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Ooi Y. M., Weiss M. A., Hsu A., Ooi B. S. Mechanisms of suppression of mouse mesangial cell proliferation by macrophage supernatants. J Immunol. 1983 Apr;130(4):1790–1795. [PubMed] [Google Scholar]
  32. Pardo V., Aldana M., Colton R. M., Fischl M. A., Jaffe D., Moskowitz L., Hensley G. T., Bourgoignie J. J. Glomerular lesions in the acquired immunodeficiency syndrome. Ann Intern Med. 1984 Oct;101(4):429–434. doi: 10.7326/0003-4819-101-4-429. [DOI] [PubMed] [Google Scholar]
  33. Pardo V., Meneses R., Ossa L., Jaffe D. J., Strauss J., Roth D., Bourgoignie J. J. AIDS-related glomerulopathy: occurrence in specific risk groups. Kidney Int. 1987 May;31(5):1167–1173. doi: 10.1038/ki.1987.124. [DOI] [PubMed] [Google Scholar]
  34. Rao T. K., Filippone E. J., Nicastri A. D., Landesman S. H., Frank E., Chen C. K., Friedman E. A. Associated focal and segmental glomerulosclerosis in the acquired immunodeficiency syndrome. N Engl J Med. 1984 Mar 15;310(11):669–673. doi: 10.1056/NEJM198403153101101. [DOI] [PubMed] [Google Scholar]
  35. Rao T. K., Friedman E. A., Nicastri A. D. The types of renal disease in the acquired immunodeficiency syndrome. N Engl J Med. 1987 Apr 23;316(17):1062–1068. doi: 10.1056/NEJM198704233161705. [DOI] [PubMed] [Google Scholar]
  36. Rao T. K. Human immunodeficiency virus (HIV) associated nephropathy. Annu Rev Med. 1991;42:391–401. doi: 10.1146/annurev.me.42.020191.002135. [DOI] [PubMed] [Google Scholar]
  37. Rao T. K., Nicastri A. D., Friedman E. A. Natural history of heroin-associated nephropathy. N Engl J Med. 1974 Jan 3;290(1):19–23. doi: 10.1056/NEJM197401032900105. [DOI] [PubMed] [Google Scholar]
  38. Rennke H. G., Klein P. S. Pathogenesis and significance of nonprimary focal and segmental glomerulosclerosis. Am J Kidney Dis. 1989 Jun;13(6):443–456. doi: 10.1016/s0272-6386(89)80001-0. [DOI] [PubMed] [Google Scholar]
  39. Saito T., Atkins R. C. Contribution of mononuclear leucocytes to the progression of experimental focal glomerular sclerosis. Kidney Int. 1990 Apr;37(4):1076–1083. doi: 10.1038/ki.1990.88. [DOI] [PubMed] [Google Scholar]
  40. Schreiner G. F., Cotran R. S., Pardo V., Unanue E. R. A mononuclear cell component in experimental immunological glomerulonephritis. J Exp Med. 1978 Feb 1;147(2):369–384. doi: 10.1084/jem.147.2.369. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Schreiner G. F., Cotran R. S., Unanue E. R. Modulation of Ia and leukocyte common antigen expression in rat glomeruli during the course of glomerulonephritis and aminonucleoside nephrosis. Lab Invest. 1984 Nov;51(5):524–533. [PubMed] [Google Scholar]
  42. Schreiner G. F. The mesangial phagocyte and its regulation of contractile cell biology. J Am Soc Nephrol. 1992 Apr;2(10 Suppl):S74–S82. doi: 10.1681/ASN.V210s74. [DOI] [PubMed] [Google Scholar]
  43. Schreiner G. F. The role of the macrophage in glomerular injury. Semin Nephrol. 1991 May;11(3):268–275. [PubMed] [Google Scholar]
  44. Singhal P. C., Gibbons N., Abramovici M. Long term effects of morphine on mesangial cell proliferation and matrix synthesis. Kidney Int. 1992 Jun;41(6):1560–1570. doi: 10.1038/ki.1992.226. [DOI] [PubMed] [Google Scholar]
  45. Torbohm I., Berger B., Schönermark M., von Kempis J., Rother K., Hänsch G. M. Modulation of collagen synthesis in human glomerular epithelial cells by interleukin 1. Clin Exp Immunol. 1989 Mar;75(3):427–431. [PMC free article] [PubMed] [Google Scholar]
  46. Treser G., Cherubin C., Longergan E. T., Yoshizawa N., Viswanathan V., Tannenberg A. M., Pompa D., Lange K. Renal lesions in narcotic addicts. Am J Med. 1974 Nov;57(5):687–694. doi: 10.1016/0002-9343(74)90842-0. [DOI] [PubMed] [Google Scholar]
  47. Wesson L. G. Compensatory growth and other growth responses of the kidney. Nephron. 1989;51(2):149–184. doi: 10.1159/000185282. [DOI] [PubMed] [Google Scholar]
  48. van Goor H., van der Horst M. L., Fidler V., Grond J. Glomerular macrophage modulation affects mesangial expansion in the rat after renal ablation. Lab Invest. 1992 May;66(5):564–571. [PubMed] [Google Scholar]

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