Induction of Chronic Progressive Glomerulonephritis with Immunofluorescent ‘Mesangial Pattern’ in Rats

Abstract

Morphologic changes of extracapillary and chronic progressive glomerulonephritis with contracted kidneys, resembling those of adult human chronic glomerulonephritis, were induced in rats by a single injection of the purified glycopeptide and Freund’s incomplete adjuvant into the hind footpads. The purified glycopeptide was prepared by TCA treatment or DEAE-cellulose chromatography from the nephritogenic glycopeptide which is known to have the ability to induce typical morphologic changes of membranous glomerulonephritis. As demonstrated in this report, the purification procedures result in complete elimination of contaminating free amino acids from the nephritogenic glycopeptide. The basic pathogenesis of the new experimental model of proliferative glomerulonephritis (including typical chronic glomerulonephritis) appears to have other than immune complex mechanisms.

Nephritogenic Glycoprotein

“…Morphological changes in concurrent positive control group VI injected with natural nephritogenoside were those of chronic glomerulonephritis as those previously reported [6][7][8]. The careful examination led to the dis covery of myeloid bodies deposited in glomerular ep ithelial cells.…”

“…We have previously reported that a single footpad injection of a homologous renal glycopeptide (called nephritogenoside) induces in rats mesangial proliferative glomerulonephritis (PGN) with a pattern of mesangial immunofluorescence [1][2][3][4], which results in sclerosing glomerulonephritis (end-stage kidney), 6-8 months after injection [5][6][7], This finding has been supported by Nishii et al [8].…”

“…Myeloid bodies were not present in the kidney of group IV and V animals. [Note: It should be emphasized that retrospective investigation of the morphological changes of the kidney in nephritis rats produced by a single footpad injection of natural nephritogenoside [6,7] re vealed the presence of myeloid bodies in the epithelial cells of glomeruli (the podocytes). ]…”

“…Chemically, the active portion of nephritogenoside has been found to be in the carbohydrate moiety [11], and the nephritogenic activity of this glycopeptide is not decreased by exhaustive digestion with proteolytic en zymes [5,6,12], Thus, we have investigated the chemical structure (especially, the sugar portion) of nephritogenoside on a molecular level and proposed the following structure [13][14][15]: a-Glc-(l-»6)-P-Glc-(l-*6)-a-Glc-(l-NHCO-peptide).…”

Nephritogenic Glycoprotein

“…Previously, strikingly similar results have been obtained in the experiments using renal glycopeptide that was isolated and purified from nephritogenic renal glycoprotein (ob tained from the trypsin digests) by further proteolytic digestion (72 h) with pronase [16][17][18], Consequently, the procedure -pronase di gestion followed by T C A treatment -seems to have an ability to isolate from rat kidney the glycopeplide that possesses no antigenic activ ity with respect to producing nephrotoxic anti body (kidney-fixing antibody), but has an abil ity when combined with Freund's incomplete adjuvant to induce proliferative glomerulo nephritis (with an immunofluorescenl mesan gial pattern) in rats (homologous animals) by a single injection into the hind footpads.…”