Differentiating Glomerular Inflammation from Fibrosis in a Bone Marrow Chimera for Rat Anti-Glomerular Basement Membrane Glomerulonephritis.
BACKGROUND
Many types of glomerulonephritis (GN) undergo tandem connected phases: inflammation and fibrosis. Fibrosis in human GNs leads to irreversible end-stage disease. This study investigated how these 2 phases were controlled.


METHODS
Using a rat anti-glomerular basement membrane GN model, we established bone marrow (BM) chimeras between GN-resistant Lewis (LEW) and GN-susceptible Wistar Kyoto (WKY) rats. Glomerular inflammation and fibrosis were compared between chimeras.


RESULTS
LEW's BM to WKY chimeras with or without co-transfer of host WKY's T cells were GN-resistant. On the other hand, WKY's BM to LEW (LEW(WKY)) chimeras developed glomerular inflammation and albuminuria upon immunization. Quantitative analysis showed that the number and composition of inflammatory cells in glomeruli of immunized LEW(WKY) chimeras were similar to those in immunized WKY rats at their inflammatory peak. Thus, glomerular inflammation was controlled by BM-derived non-T cell populations. However, unlike WKY rats, LEW(WKY) rats did not develop fibrosis until the end of experiments (84 days) in spite of persistent inflammation and albuminuria.


CONCLUSIONS
Inflammation alone was not sufficient to trigger fibrosis, suggesting a critical role of glomerular cells in the fibrotic process. As LEW(WKY) chimera allows us to separate glomerular inflammation from fibrosis, this model provides a useful tool to study how fibrosis is initiated following inflammation.
Cindy
C
Zhou
Kristie
K
Lou
Kiana
K
Tatum
Jeremiah
J
Funk
Jean
J
Wu
Todd
T
Bartkowiak
David
D
Kagan
Yahuan
Y
Lou
D000419:Albuminuria / Q000276:immunology; D000818:Animals; D019867:Anti-Glomerular Basement Membrane Disease / Q000276:immunology* / Q000473:pathology*; D001806:Blood Urea Nitrogen; D016026:Bone Marrow Transplantation; D002678:Chimera; D024141:Collagen Type IV / Q000276:immunology; D003404:Creatinine / Q000097:blood; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D005355:Fibrosis; D007678:Kidney Glomerulus / Q000473:pathology*; D022423:Myeloid Cells / Q000276:immunology* / Q000637:transplantation; D010446:Peptide Fragments / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D011921:Rats, Inbred WKY; D013601:T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D013997:Time Factors
D024141:Collagen Type IV; D018984:Epitopes, T-Lymphocyte; D010446:Peptide Fragments; C000608266:collagen 4alpha3 chain (28-40), rat; D003404:Creatinine