Role of mast cells in experimental anti-glomerular basement membrane glomerulonephritis

Eur J Immunol. 2005 Oct;35(10):3074-82. doi: 10.1002/eji.200526250.


Recently, divergent reports on the role of mast cells (MC) in different glomerular diseases have brought our attention to their role in an accelerated model of anti-glomerular basement membrane (GBM) glomerulonephritis (GN). Genetically MC-deficient Kit(W)/Kit(W-v) mice, MC-reconstituted Kit(W)/Kit(W-v) mice and Kit+/+ control mice were subjected to anti-GBM GN. Kit(+/+) mice developed moderate proteinuria and glomerular damage following the induction of anti-GBM nephritis. In contrast, proteinuria and glomerular damage were dramatically increased in MC-deficient Kit(W)/Kit(W-v) mice. MC-reconstituted Kit(W)/Kit(W-v) mice showed proteinuria and glomerular damage comparable to Kit+/+ mice. A significant increase in infiltrating T cells and macrophages was detected in MC-deficient Kit(W)/Kit(W-v) mice as compared to Kit+/+ control mice and MC-reconstituted Kit(W)/Kit(W-v) mice. Accordingly, we observed an increase of TGF-beta1 mRNA in kidneys from Kit(W)/Kit(W-v) mice. Interestingly, we did not detect MC in the kidney using either Giemsa staining or RT-real-time PCR, but MC were found in the regional lymph nodes. Finally, mortality of Kit(W)/Kit(W-v) mice was significantly increased after the induction of anti-GBM GN due to uremia. Our report provides the first direct evidence that MC are protective in anti-GBM GN, possibly by modulating the influx of effector T cells and macrophages to inflammatory sites in the kidney.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Glomerular Basement Membrane Disease / immunology*
  • Anti-Glomerular Basement Membrane Disease / pathology*
  • CD4-Positive T-Lymphocytes / immunology
  • Disease Models, Animal
  • Lymph Nodes / cytology
  • Lymph Nodes / immunology
  • Macrophages / immunology
  • Mast Cells / immunology*
  • Mice
  • Mice, Mutant Strains
  • RNA, Messenger / analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Serine Endopeptidases / biosynthesis
  • Serine Endopeptidases / immunology
  • Transforming Growth Factor beta / immunology
  • Transforming Growth Factor beta / metabolism
  • Transforming Growth Factor beta1
  • Tryptases


  • RNA, Messenger
  • Tgfb1 protein, mouse
  • Tpsb2 protein, mouse
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • Serine Endopeptidases
  • Tpsab1 protein, mouse
  • Tryptases