Granulomatous transformation of capillary lesions in pulmonary-renal syndrome autologously induced anti-glomerular basement membrane disease in Wistar-Kyoto rats

Clin Exp Nephrol. 2010 Apr;14(2):123-31. doi: 10.1007/s10157-009-0260-9. Epub 2010 Jan 9.


Background: Pulmonary-renal syndrome is characterized by pulmonary hemorrhage and rapidly progressive glomerulonephritis in various immunological states. Histopathological analysis of pulmonary-renal syndrome is not yet complete.

Methods: Wistar-Kyoto (WKY) rats were sensitized using the noncollagenous (NC1) domain of type IV collagen from bovine kidney as an antigen. Histopathology of the kidneys and lungs was investigated with light microscopy, immunohistochemistry and electromicroscopy. Expression levels of cytokine mRNA were determined by real-time RT-PCR using renal tissue of rats.

Results: Macrophage-rich granulomatous glomerulonephritis and alveolar capillaritis accompanied with pulmonary hemorrhage were induced by the sensitization. The humoral antibody against NC1 was detected on the glomerular and alveolar capillary walls. Th2 cytokine IL-10 was dominant over Th1 cytokine IFN-gamma in renal tissues of WKY rats.

Conclusion: The granulomatous transformation seemed to be induced by macrophage conspicuous capillaritis under dominant cellular immune reactions in WKY rats. In addition to Th1 cytokines, Th2 cytokines may also participate in the formation of granulomatous lesions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Glomerular Basement Membrane Disease / pathology*
  • Glomerulonephritis / pathology*
  • Granuloma / pathology*
  • Hemorrhage / pathology*
  • Interferon-gamma / biosynthesis
  • Kidney / pathology
  • Kidney Diseases / pathology*
  • Kidney Glomerulus / pathology
  • Lung / pathology
  • Lung Diseases / pathology*
  • Rats
  • Rats, Inbred WKY
  • Tumor Necrosis Factor-alpha / biosynthesis


  • Tumor Necrosis Factor-alpha
  • Interferon-gamma