Role of mast cells in experimental anti-glomerular basement membrane glomerulonephritis.
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.
Hochegger
Kathrin
K
Innsbruck Medical University, Clinical Division of Nephrology, Innsbruck, Austria.
Siebenhaar
Frank
F
Vielhauer
Volker
V
Heininger
Dorothea
D
Mayadas
Tanya N
TN
Mayer
Gert
G
Maurer
Marcus
M
Rosenkranz
Alexander R
AR
D000818:Animals; D019867:Anti-Glomerular Basement Membrane Disease / Q000276:immunology* / Q000473:pathology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D008817:Mice, Mutant Strains; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012697:Serine Endopeptidases / Q000096:biosynthesis / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000378:metabolism; D053773:Transforming Growth Factor beta1; D053802:Tryptases
D012333:RNA, Messenger; C508961:Tgfb1 protein, mouse; C509190:Tpsb2 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D012697:Serine Endopeptidases; C509222:Tpsab1 protein, mouse; D053802:Tryptases