Induction of passive Heymann nephritis in complement component 6-deficient PVG rats

S Timothy Spicer, Giang T Tran, Murray C. Killingsworth, Nicole M Carter, David A Power, Kathy Paizis, Rochelle Boyd, Suzanne J Hodgkinson, Bruce M Hall

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Abstract

Passive Heymann nephritis (PHN), a model of human membranous nephritis, is induced in susceptible rat strains by injection of heterologous antisera to rat renal tubular Ag extract. PHN is currently considered the archetypal complement-dependent form of nephritis, with the proteinuria resulting from sublytic glomerular epithelial cell injury induced by the complement membrane attack complex (MAC) of C5b-9. This study examined whether C6 and MAC are essential to the development of proteinuria in PHN by comparing the effect of injection of anti-Fx1A antisera into PVG rats deficient in C6 (PVG/C6(-)) and normal PVG rats (PVG/c). PVG/c and PVG/C6(-) rats developed similar levels of proteinuria at 3, 7, 14, and 28 days following injection of antisera. Isolated whole glomeruli showed similar deposition of rat Ig and C3 staining in PVG/c and PVG/C6(-) rats. C9 deposition was abundant in PVG/c but was not detected in PVG/C6(-) glomeruli, indicating C5b-9/MAC had not formed in PVG/C6(-) rats. There was also no difference in the glomerular cellular infiltrate of T cells and macrophages nor the size of glomerular basement membrane deposits measured on electron micrographs. To examine whether T cells effect injury, rats were depleted of CD8+ T cells which did not affect proteinuria in the early heterologous phase but prevented the increase in proteinuria associated with the later autologous phase. These studies showed proteinuria in PHN occurs without MAC and that other mechanisms, such as immune complex size, early complement components, CD4+ and CD8+ T cells, disrupt glomerular integrity and lead to proteinuria.

Original languageEnglish
Pages (from-to)172-8
Number of pages7
JournalJournal of Immunology
Volume179
Issue number1
Publication statusPublished - 1 Jul 2007
Externally publishedYes

Keywords

  • Animals
  • Antigen-Antibody Complex
  • CD8-Positive T-Lymphocytes
  • Cell Movement
  • Complement C3
  • Complement C6
  • Complement C9
  • Complement Membrane Attack Complex
  • Disease Models, Animal
  • Glomerulonephritis, Membranous
  • Immunoglobulins
  • Kidney Cortex
  • Lymphopenia
  • Macrophages
  • Male
  • Proteinuria
  • Rats
  • Rats, Mutant Strains
  • T-Lymphocyte Subsets
  • Comparative Study
  • Journal Article
  • Research Support, Non-U.S. Gov't

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    Spicer, S. T., Tran, G. T., Killingsworth, M. C., Carter, N. M., Power, D. A., Paizis, K., ... Hall, B. M. (2007). Induction of passive Heymann nephritis in complement component 6-deficient PVG rats. Journal of Immunology, 179(1), 172-8.