Abstract
The pathogenesis of proteinuria associated with immune complex disease is incompletely understood. A quantitative electron-microscopic study was undertaken to determine the relative contribution of lesions in capillary loops and mesangial basement membrane areas and their possible correlations to urinary protein excretion data. Pathologic features including the loss of foot processes (and slit diaphragms), the formation of junctional complexes in visceral epithelium, and the distribution of immune complexes in basement membrane were assessed in glomeruli of mice with lupus nephritis. Swiss albino mice served as control animals. In control animals the distribution of split pores per unit length of basement membrane was approximately 60% higher in capillary loop compared to mesangial basement membrane areas. In mice with lupus nephritis, the reduction in the number of slit pores per unit length of basement membrane to 30% or less of normal, the formation of epithelial junctions, and the relative distribution of immune complexes were not statistically different in capillary versus mesangial basement membrane areas. Animals with murine lupus showed poorly selective proteinuria, but the correlation between features studied and extent of protein excretion was poor. The results of these studies 1) establish the relative distribution of slit pores in mesangial and peripheral loop basement membrane, 2) demonstrate that glomerular changes associated with immune complex deposition are comparable in capillary and mesangial basement membrane areas, and 3) are consistent with a focal and nonuniform alteration in glomerular permeability properties associated with immune complex disease.
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- Bohman S. O., Deguchi N., Jørgen H., Gundersen H. J., Hestbech J., Maunsbach A. B., Olsen S. Evaluation of a procedure for systematic semiquantitative analysis of glomerular ultrastructure in human renal biopsies. Lab Invest. 1979 Apr;40(4):433–434. [PubMed] [Google Scholar]
- Brenner B. M., Hostetter T. H., Humes H. D. Molecular basis of proteinuria of glomerular origin. N Engl J Med. 1978 Apr 13;298(15):826–833. doi: 10.1056/NEJM197804132981507. [DOI] [PubMed] [Google Scholar]
- Farquhar M. G. Editorial: The primary glomerular filtration barrier--basement membrane or epithelial slits? Kidney Int. 1975 Oct;8(4):197–211. doi: 10.1038/ki.1975.103. [DOI] [PubMed] [Google Scholar]
- HENRY R. J., SEGALOVE M., SOBEL C. Turbidimetric determination of proteins with sulfosalicylic and trichloracetic acids. Proc Soc Exp Biol Med. 1956 Aug-Sep;92(4):748–751. doi: 10.3181/00379727-92-22601. [DOI] [PubMed] [Google Scholar]
- Kanwar Y. S., Farquhar M. G. Anionic sites in the glomerular basement membrane. In vivo and in vitro localization to the laminae rarae by cationic probes. J Cell Biol. 1979 Apr;81(1):137–153. doi: 10.1083/jcb.81.1.137. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Karnovsky M. J. The ultrastructure of glomerular filtration. Annu Rev Med. 1979;30:213–224. doi: 10.1146/annurev.me.30.020179.001241. [DOI] [PubMed] [Google Scholar]
- Kelley V. E., Cavallo T. An ultrastructural study of the glomerular slit diaphragm in New Zealand black/white mice. Lab Invest. 1976 Sep;35(3):213–220. [PubMed] [Google Scholar]
- Kelley V. E., Cavallo T. Glomerular permeability. Ultrastructural studies in New Zealand black/white mice using polyanionic ferritin as a molecular probe. Lab Invest. 1977 Sep;37(3):265–275. [PubMed] [Google Scholar]
- Kelley V. E., Cavallo T. Glomerular permeability: focal loss of anionic sites in glomeruli of proteinuric mice with lupus nephritis. Lab Invest. 1980 Jan;42(1):59–64. [PubMed] [Google Scholar]
- Lambert P. H., Dixon F. J. Pathogenesis of the glomerulonephritis of NZB/W mice. J Exp Med. 1968 Mar 1;127(3):507–522. doi: 10.1084/jem.127.3.507. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Osterby R. Quantitative electron microscopy of the glomerular basement membrane. A methodologic study. Lab Invest. 1971 Jul;25(1):15–24. [PubMed] [Google Scholar]
- Pesce A. J. Methods used for the analysis of proteins in the urine. Nephron. 1974;13(1):93–104. doi: 10.1159/000180371. [DOI] [PubMed] [Google Scholar]
- Pinto J. A., Brewer D. B. Combined light and electron-microscope morphometric studies of acute puromycin aminonucleoside nephropathy in rats. J Pathol. 1975 Jul;116(3):149–164. doi: 10.1002/path.1711160304. [DOI] [PubMed] [Google Scholar]
- Pinto J. A., Brewer D. B. Glomerular morphometry. I. Combined light and electron microscope studies in normal rats. Lab Invest. 1974 May;30(5):657–663. [PubMed] [Google Scholar]
- Powell H. R. Relationship between proteinuria and epithelial cell changes in minimal lesion glomerulopathy. Nephron. 1976;16(4):310–317. doi: 10.1159/000180616. [DOI] [PubMed] [Google Scholar]
- REYNOLDS E. S. The use of lead citrate at high pH as an electron-opaque stain in electron microscopy. J Cell Biol. 1963 Apr;17:208–212. doi: 10.1083/jcb.17.1.208. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rennke H. G., Venkatachalam M. A. Glomerular permeability of macromolecules. Effect of molecular configuration on the fractional clearance of uncharged dextran and neutral horseradish peroxidase in the rat. J Clin Invest. 1979 Apr;63(4):713–717. doi: 10.1172/JCI109354. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schneeberger E. E., Leber P. D., Karnovsky M. J., McCluskey R. T. Altered functional properties of the renal glomerulus in autologous immune complex nephritis: an ultrastructural tracer study. J Exp Med. 1974 May 1;139(5):1283–1302. doi: 10.1084/jem.139.5.1283. [DOI] [PMC free article] [PubMed] [Google Scholar]


