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Immunology and Pathology
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Oral Administration of Glomerular Basement Membrane Prevents the Development of Experimental Autoimmune Glomerulonephritis in the WKY Rat

JOHN REYNOLDS and CHARLES D. PUSEY
JASN January 2001, 12 (1) 61-70;
JOHN REYNOLDS
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CHARLES D. PUSEY
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    Figure 1.

    Effect of oral administration of glomerular basement membrane (GBM) on circulating anti-GBM antibody concentrations in groups of WKY rats (n = 5 to 6) with experimental autoimmune glomerulonephritis (EAG). Results shown represent the mean of each group: positive control ([UNK]), GBM 0.5 mg (▪), GBM 2.5 mg (□), or GBM 5 mg (▴), and negative control (○). *, P < 0.01 (positive control versus GBM 5 mg).

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    Figure 2.

    Effect of oral administration of GBM on circulating levels of IgG1 (A), IgG2a (B), and ratio of IgG1/IgG2a anti-GBM antibodies (C) in groups of WKY rats (n = 5 to 6) with EAG. Results shown represent the mean ± SD of each group at week 4 after immunization. *, P < 0.01 (positive control versus GBM 5 mg).

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    Figure 3.

    Direct immunofluorescence of kidney tissue at week 4 in WKY rats with EAG showing strong linear deposition of IgG along the GBM in a positive control animal (A), marked reduction in the deposition of IgG in an animal given GBM orally at 5 mg (B), large deposits of fibrin within the glomeruli of a positive control animal (C), and negative findings for fibrin in an animal given GBM orally at 5 mg (D). Magnification, ×300.

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    Figure 4.

    Effect of oral administration of GBM on albuminuria in groups of WKY rats (n = 5 to 6) with EAG. Results shown represent the mean of each group: positive control ([UNK]), GBM 0.5 mg (▪), GBM 2.5 mg (□), or GBM 5 mg (▴), and negative control (○). *, P < 0.01 (positive control versus GBM 2.5 mg); **, P < 0.001 (positive control versus GBM 5 mg).

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    Figure 5.

    Effect of oral administration of GBM on creatinine clearance in groups of WKY rats (n = 5 to 6) with EAG. Results shown represent the mean ± SD of each group at week 4 after immunization. *, P < 0.01 (positive control versus GBM 5 mg).

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    Figure 6.

    Effect of oral administration of GBM on renal histology at week 4 in groups of WKY rats (n = 5 to 6) with EAG. Results shown represent the severity of glomerular abnormalities, which were graded as normal, abnormal, or severe (>50% of the glomerulus affected by necrosis/crescent formation). *, P < 0.01 (positive control versus GBM 2.5 mg; **, P < 0.001 (positive control versus GBM 5 mg).

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    Figure 8.

    Light microscopy of kidney tissue at week 4 in WKY rats with EAG showing marked segmental necrosis of the glomerular tuft with crescent formation in a positive control animal (A; hematoxylin and eosin), mild segmental proliferation in an animal given GBM orally at 5 mg (B; hematoxylin and eosin), large numbers of macrophages infiltrating the glomeruli and interstitium in a positive control animal (C; immunoperoxidase), and reduced numbers of macrophages in an animal given GBM orally at 5 mg (D; immunoperoxidase). Magnification, ×300.

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    Figure 7.

    Effect of oral administration of GBM on the numbers of CD8+ T cells (A) and macrophages (B) detected by immunoperoxidase staining of kidney tissue in groups of WKY rats (n = 5 to 6) with EAG. Results shown represent the mean ± SD of each group at week 4 after immunization. *, P < 0.01 (positive control versus GBM 5 mg).

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    Figure 9.

    Effect of oral administration of GBM on in vitro proliferation of splenic T cells pooled from different groups of WKY rats with EAG. Results shown represent the mean ± SD of each group at week 4 after immunization. *, P < 0.01 (positive control versus GBM 5 mg).

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    Table 1.

    Effects of oral administration of GBM to WKY rats with EAG on deposition of IgG on the GBM and deposition of fibrin in the glomeruli. Results are expressed as intensity of fluorescence at week 4 in individual animals

    Intensity of Immunostaining
    3+2+1+—
    IgG
    positive control (n = 6)3300
    negative control (n = 5)0005
    GBM 0.5 mg (n = 6)4200
    GBM 2.5 mg (n = 5)0320
    GBM 5 mg (n = 6)0123
    Fibrin
    positive control (n = 6)4200
    negative control (n = 5)0005
    GBM 0.5 mg (n = 6)3300
    GBM 2.5 mg (n = 5)1220
    GBM 5 mg (n = 6)0015
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Journal of the American Society of Nephrology: 12 (1)
Journal of the American Society of Nephrology
Vol. 12, Issue 1
1 Jan 2001
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Oral Administration of Glomerular Basement Membrane Prevents the Development of Experimental Autoimmune Glomerulonephritis in the WKY Rat
JOHN REYNOLDS, CHARLES D. PUSEY
JASN Jan 2001, 12 (1) 61-70;

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Oral Administration of Glomerular Basement Membrane Prevents the Development of Experimental Autoimmune Glomerulonephritis in the WKY Rat
JOHN REYNOLDS, CHARLES D. PUSEY
JASN Jan 2001, 12 (1) 61-70;
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More in this TOC Section

  • The Parietal Epithelial Cell: A Key Player in the Pathogenesis of Focal Segmental Glomerulosclerosis in Thy-1.1 Transgenic Mice
  • Gene Therapy via Blockade of Monocyte Chemoattractant Protein-1 for Renal Fibrosis
  • Contributions of IL-1β and IL-1α to Crescentic Glomerulonephritis in Mice
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Cited By...

  • A Nephritogenic Peptide Induces Intermolecular Epitope Spreading on Collagen IV in Experimental Autoimmune Glomerulonephritis
  • T Cells in Crescentic Glomerulonephritis
  • Distinct Epitopes for Anti-Glomerular Basement Membrane Alport Alloantibodies and Goodpasture Autoantibodies within the Noncollagenous Domain of {alpha}3(IV) Collagen: A Janus-Faced Antigen
  • IL-12p40 and IL-18 in Crescentic Glomerulonephritis: IL-12p40 is the Key Th1-Defining Cytokine Chain, Whereas IL-18 Promotes Local Inflammation and Leukocyte Recruitment
  • Nasal Administration of Recombinant Rat {alpha}3(IV)NC1 Prevents the Development of Experimental Autoimmune Glomerulonephritis in the WKY Rat
  • Point Mutations of Single Amino Acids Abolish Ability of {alpha}3 NC1 Domain to Elicit Experimental Autoimmune Glomerulonephritis in Rats
  • Anti-CD8 Monoclonal Antibody Therapy Is Effective in the Prevention and Treatment of Experimental Autoimmune Glomerulonephritis
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