Interferon gamma-mediated renal MHC expression in mercuric chloride-induced glomerulonephritis.
In rodents, mercuric chloride (HgCl2) causes an autoimmune disorder with glomerulonephritis (GN), and represents an animal model for the pathogenesis of GN. We have tested the hypothesis that HgCl2 induces major histocompatibility complex (MHC) expression in renal parenchymal cells, and studied the kinetics of this induction and its temporal relation to the development of immune complex deposition in the glomeruli. Mice treated with doses of HgCl2 between 2 and 3.2 mg/kg three times for one week had increased renal expression of MHC class I and class II (at the mRNA and the product levels). Class I induction was observed in proximal tubule cells, endothelial cells and glomerular cells. Class II induction was seen mainly in interstitial cells and, to a lesser extent, in tubule cells. Renal MHC expression was maximal at one week, decreased progressively after the second week of HgCl2 administration, and reached basal levels by 23 weeks. In contrast, the amount of lymphocyte infiltration in the kidney increased from the first to the fifth week and was followed by the appearance of glomerular immune deposits from the third week on. Glomerular immune complex deposits were maximal at five weeks and, by 23 weeks, immune deposits in HgCl2-treated mice were only slightly increased over those observed in the sham group. Renal MHC induction by HgCl2 was significantly reduced by treatment with monoclonal antibody against interferon gamma.(ABSTRACT TRUNCATED AT 250 WORDS)
Madrenas
J
J
Department of Immunology, University of Alberta, Edmonton, Canada.
Parfrey
N A
NA
Halloran
P F
PF
D000818:Animals; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D005921:Glomerulonephritis / Q000139:chemically induced* / Q000276:immunology; D007105:Immune Complex Diseases / Q000139:chemically induced* / Q000276:immunology; D007124:Immunoenzyme Techniques; D007371:Interferon-gamma / Q000276:immunology*; D007668:Kidney / Q000276:immunology*; D007678:Kidney Glomerulus / Q000276:immunology; D008285:Major Histocompatibility Complex / Q000235:genetics*; D008297:Male; D008627:Mercuric Chloride; D051379:Mice; D008815:Mice, Inbred Strains; D012333:RNA, Messenger / Q000235:genetics*
D012333:RNA, Messenger; D008627:Mercuric Chloride; D007371:Interferon-gamma