Factors affecting the glomerular protein leak after polyclonal activation in the HgCl2-induced model of anti-GBM disease in the brown Norway rat.
The administration of the polyclonal activator HgCl2 (1 mg/kg i.p.) to Brown Norway (BN) rats on days 0, 2, 4 and 7 resulted in the cyclical production of anti-glomerular basement membrane (GBM) antibodies, the first peak of which occurred at day 14 with a smaller peak at day 26. Glomerular anti-GBM antibody levels were also raised at day 14. Renal injury as measured by urinary loss of albumin and complement (C3) was also cyclical, being maximal on days 15 and 23-26. However, urinary protein excretion was significantly diminished on the days corresponding to the first peak of circulating antibody levels if peripheral monocyte counts were reduced by the repeated injection of anti-monocyte antiserum. Protein excretion was also reduced after the administration of anti-polymorphonuclear neutrophil (PMN) antiserum. Finally, glomerular protein excretion was independent of depletion of serum C3 levels to less than 10% of pooled normal sera by the repeated administration of Cobra Venom Factor (CVF) on days 9 and 11. These findings demonstrate that in the absence of progressive tissue injury in this model, glomerular protein excretion fluctuates according to circulating levels of anti-GBM antibody and that, despite being independent of complement, tissue injury may be increased in the presence of complement activation.
Clinical Immunology Unit, Royal Postgraduate Medical School, London, UK.
J A
JA
Savige
C M
CM
Lockwood
D000818:Animals; D001323:Autoantibodies / Q000032:analysis; D001327:Autoimmune Diseases / Q000276:immunology*; D001485:Basement Membrane / Q000276:immunology; D003176:Complement C3 / Q000172:deficiency; D004195:Disease Models, Animal; D005921:Glomerulonephritis / Q000276:immunology*; D007678:Kidney Glomerulus / Q000276:immunology*; D007958:Leukocyte Count; D008627:Mercuric Chloride; D011507:Proteinuria / Q000276:immunology*; D051381:Rats; D011914:Rats, Inbred BN
D001323:Autoantibodies; D003176:Complement C3; D008627:Mercuric Chloride