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. 1995 Jul;147(1):25–32.

Human immunodeficiency virus-1 gp120 and gp160 envelope proteins modulate mesangial cell gelatinolytic activity.

P C Singhal 1, S Sagar 1, D Chandra 1, P Garg 1
PMCID: PMC1869868  PMID: 7604883

Abstract

Patients with human immunodeficiency virus (HIV) infection often develop glomerular lesions (mesangial expansion and sclerosis). Modulation of matrix degradation may be important in the expansion of the mesangium. We studied the effect of HIV sera and HIV-1 envelope glycoproteins on gelatinolytic activity of human mesangial cells. HIV serum-treated cells showed lower (P < 0.01) gelatinolytic activity when compared with cells treated with control serum (control serum, 4.3 +/- 0.1 versus HIV serum, 3.3 +/- 0.1 micrograms gelatin degraded/mg protein). Mesangial cells incubated with HIV-1 gp120 protein also showed decreased (P < 0.01) gelatinolytic activity (control, 4.6 +/- 0.2 versus HIV-1 gp120 protein, 1.7 +/- 0.2 micrograms gelatin degraded/mg protein). HIV-1 gp160 protein also inhibited (P < 0.05) mesangial cell gelatinolytic activity as judged by a biotin-avidin assay as well as by a 3H gelatin degradation assay. In contrast, gp alpha-1 acid, a nonviral glycoprotein, did not modulate mesangial cell gelatinolytic activity. These results suggest that the serum contents of HIV patients decrease gelatinolytic activity of mesangial cells. This effect of HIV sera seems to be mediated through HIV-1 gp proteins.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Border W. A., Ruoslahti E. Transforming growth factor-beta in disease: the dark side of tissue repair. J Clin Invest. 1992 Jul;90(1):1–7. doi: 10.1172/JCI115821. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bourgoignie J. J., Pardo V. The nephropathology in human immunodeficiency virus (HIV-1) infection. Kidney Int Suppl. 1991 Dec;35:S19–S23. [PubMed] [Google Scholar]
  3. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1016/0003-2697(76)90527-3. [DOI] [PubMed] [Google Scholar]
  4. Cawston T. E., Barrett A. J. A rapid and reproducible assay for collagenase using [1-14C]acetylated collagen. Anal Biochem. 1979 Nov 1;99(2):340–345. doi: 10.1016/s0003-2697(79)80017-2. [DOI] [PubMed] [Google Scholar]
  5. Clouse K. A., Cosentino L. M., Weih K. A., Pyle S. W., Robbins P. B., Hochstein H. D., Natarajan V., Farrar W. L. The HIV-1 gp120 envelope protein has the intrinsic capacity to stimulate monokine secretion. J Immunol. 1991 Nov 1;147(9):2892–2901. [PubMed] [Google Scholar]
  6. 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]
  7. Dickie P., Felser J., Eckhaus M., Bryant J., Silver J., Marinos N., Notkins A. L. HIV-associated nephropathy in transgenic mice expressing HIV-1 genes. Virology. 1991 Nov;185(1):109–119. doi: 10.1016/0042-6822(91)90759-5. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. 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]
  10. Ho D. D., Neumann A. U., Perelson A. S., Chen W., Leonard J. M., Markowitz M. Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection. Nature. 1995 Jan 12;373(6510):123–126. doi: 10.1038/373123a0. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. Kekow J., Wachsman W., McCutchan J. A., Cronin M., Carson D. A., Lotz M. Transforming growth factor beta and noncytopathic mechanisms of immunodeficiency in human immunodeficiency virus infection. Proc Natl Acad Sci U S A. 1990 Nov;87(21):8321–8325. doi: 10.1073/pnas.87.21.8321. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kimmel P. L., Phillips T. M., Ferreira-Centeno A., Farkas-Szallasi T., Abraham A. A., Garrett C. T. HIV-associated immune-mediated renal disease. Kidney Int. 1993 Dec;44(6):1327–1340. doi: 10.1038/ki.1993.386. [DOI] [PubMed] [Google Scholar]
  14. Kopp J. B., Klotman M. E., Adler S. H., Bruggeman L. A., Dickie P., Marinos N. J., Eckhaus M., Bryant J. L., Notkins A. L., Klotman P. E. Progressive glomerulosclerosis and enhanced renal accumulation of basement membrane components in mice transgenic for human immunodeficiency virus type 1 genes. Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1577–1581. doi: 10.1073/pnas.89.5.1577. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Latta H., Fligiel S. Mesangial fenestrations, sieving, filtration, and flow. Lab Invest. 1985 Jun;52(6):591–598. [PubMed] [Google Scholar]
  16. Latta H. The glomerular cappillary wall. J Ultrastruct Res. 1970 Sep;32(5):526–544. doi: 10.1016/s0022-5320(70)80026-0. [DOI] [PubMed] [Google Scholar]
  17. Lovett D. H., Sterzel R. B., Kashgarian M., Ryan J. L. Neutral proteinase activity produced in vitro by cells of the glomerular mesangium. Kidney Int. 1983 Feb;23(2):342–349. doi: 10.1038/ki.1983.25. [DOI] [PubMed] [Google Scholar]
  18. Martin J., Davies M., Thomas G., Lovett D. H. Human mesangial cells secrete a GBM-degrading neutral proteinase and a specific inhibitor. Kidney Int. 1989 Nov;36(5):790–801. doi: 10.1038/ki.1989.264. [DOI] [PubMed] [Google Scholar]
  19. Mattana J., Abramovici M., Singhal P. C. Effects of human immunodeficiency virus sera and macrophage supernatants on mesangial cell proliferation and matrix synthesis. Am J Pathol. 1993 Sep;143(3):814–822. [PMC free article] [PubMed] [Google Scholar]
  20. Merrill J. E., Chen I. S. HIV-1, macrophages, glial cells, and cytokines in AIDS nervous system disease. FASEB J. 1991 Jul;5(10):2391–2397. doi: 10.1096/fasebj.5.10.2065887. [DOI] [PubMed] [Google Scholar]
  21. Michael A. F., Keane W. F., Raij L., Vernier R. L., Mauer S. M. The glomerular mesangium. Kidney Int. 1980 Feb;17(2):141–154. doi: 10.1038/ki.1980.18. [DOI] [PubMed] [Google Scholar]
  22. Oyaizu N., Chirmule N., Ohnishi Y., Kalyanaraman V. S., Pahwa S. Human immunodeficiency virus type 1 envelope glycoproteins gp120 and gp160 induce interleukin-6 production in CD4+ T-cell clones. J Virol. 1991 Nov;65(11):6277–6282. doi: 10.1128/jvi.65.11.6277-6282.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. 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]
  24. Pesce C. M., Striker L. J., Peten E., Elliot S. J., Striker G. E. Glomerulosclerosis at both early and late stages is associated with increased cell turnover in mice transgenic for growth hormone. Lab Invest. 1991 Nov;65(5):601–605. [PubMed] [Google Scholar]
  25. 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]
  26. Reckelhoff J. F., Baylis C. Glomerular metalloprotease activity in the aging rat kidney: inverse correlation with injury. J Am Soc Nephrol. 1993 May;3(11):1835–1838. doi: 10.1681/ASN.V3111835. [DOI] [PubMed] [Google Scholar]
  27. Robinson W. E., Jr, Montefiori D. C., Mitchell W. M. Antibody-dependent enhancement of human immunodeficiency virus type 1 infection. Lancet. 1988 Apr 9;1(8589):790–794. doi: 10.1016/s0140-6736(88)91657-1. [DOI] [PubMed] [Google Scholar]
  28. Sharma K., Ziyadeh F. N. The transforming growth factor-beta system and the kidney. Semin Nephrol. 1993 Jan;13(1):116–128. [PubMed] [Google Scholar]
  29. Singhal P. C., Pan C., Gibbons N. Effect of morphine on uptake of immunoglobulin G complexes by mesangial cells and macrophages. Am J Physiol. 1993 May;264(5 Pt 2):F859–F866. doi: 10.1152/ajprenal.1993.264.5.F859. [DOI] [PubMed] [Google Scholar]
  30. Sraer J. D., Adida C., Peraldi M. N., Rondeau E., Kanfer A. Species-specific properties of the glomerular mesangium. J Am Soc Nephrol. 1993 Jan;3(7):1342–1350. doi: 10.1681/ASN.V371342. [DOI] [PubMed] [Google Scholar]
  31. Wilkinson M. J., Cohen R. L., Shuman M. A. A nonradioactive assay for type IV collagen degradation. Anal Biochem. 1990 Mar;185(2):294–296. doi: 10.1016/0003-2697(90)90295-k. [DOI] [PubMed] [Google Scholar]

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