TY - JOUR
T1 - Influence of genetics on the nephritogenic potential of proteoglycans
AU - Lelongt, Brigitte
AU - Kashihara, Naoki
AU - Makino, Hirofumi
AU - Kanwar, Yashpal S.
PY - 1992/9
Y1 - 1992/9
N2 - Nephritogenic potential of antibodies directed against one of the glomerular basement membrane (GBM) components, i.e., heparan sulfate-proteoglycan (HS-PG), was investigated in different strain of rats, i.e., Brown Norway, Lewis, Long Evans, and Sprague-Dawley. The rats were given two intravenous injections of anti-HS-PG antibody on days 1 and 3, and killed 2 to 8 weeks later. Before killing, blood and urine were collected for determination of anti-rabbit IgG levels and excretion of proteins, respectively. In addition, the right kidney was perfused with 125I-anti-rat IgG to quantitate the amount of immune-complexes present within the GBM. The tissues were processed for morphologic, autoradiographic, and imunofluorescent studies. The anti-HS-PG antibody was seen uniformly bound to GBM equally in all strains of rats. However, the protein-uric response was as follows: Brown Norway ⋙ Lewis ≫ Long Evans > Sprague Daley. Also, the glomerular cells, monocytes in the glomerular capillaries, immunoreactivity of rat IgG and C3, frequency of subepithelial immune deposits, serum levels of anti-rabbit IgG, and the amount of 125I-anti-rat IgG bound to the GBM were proportionately increased among different strains of rats. The data suggest that the sustained presence of anti-HS-PG antibodies in the subepithelial aspect of the GBM with differential humoral response in the production of the antibody by the host most likely attributed to the variable glomerular damage in different strains of rats. Thus, it seems that the genetic makeup of a given strain of rat heavily influences the nephritogenic potential of an antibody and consequentially the outcome of the immune complex-mediated glomerular injury.
AB - Nephritogenic potential of antibodies directed against one of the glomerular basement membrane (GBM) components, i.e., heparan sulfate-proteoglycan (HS-PG), was investigated in different strain of rats, i.e., Brown Norway, Lewis, Long Evans, and Sprague-Dawley. The rats were given two intravenous injections of anti-HS-PG antibody on days 1 and 3, and killed 2 to 8 weeks later. Before killing, blood and urine were collected for determination of anti-rabbit IgG levels and excretion of proteins, respectively. In addition, the right kidney was perfused with 125I-anti-rat IgG to quantitate the amount of immune-complexes present within the GBM. The tissues were processed for morphologic, autoradiographic, and imunofluorescent studies. The anti-HS-PG antibody was seen uniformly bound to GBM equally in all strains of rats. However, the protein-uric response was as follows: Brown Norway ⋙ Lewis ≫ Long Evans > Sprague Daley. Also, the glomerular cells, monocytes in the glomerular capillaries, immunoreactivity of rat IgG and C3, frequency of subepithelial immune deposits, serum levels of anti-rabbit IgG, and the amount of 125I-anti-rat IgG bound to the GBM were proportionately increased among different strains of rats. The data suggest that the sustained presence of anti-HS-PG antibodies in the subepithelial aspect of the GBM with differential humoral response in the production of the antibody by the host most likely attributed to the variable glomerular damage in different strains of rats. Thus, it seems that the genetic makeup of a given strain of rat heavily influences the nephritogenic potential of an antibody and consequentially the outcome of the immune complex-mediated glomerular injury.
UR - http://www.scopus.com/inward/record.url?scp=0026706322&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0026706322&partnerID=8YFLogxK
M3 - Article
C2 - 1519664
AN - SCOPUS:0026706322
SN - 0002-9440
VL - 141
SP - 561
EP - 569
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 3
ER -