title: Role of mast cells in experimental anti-glomerular basement membrane glomerulonephritis.
abstract: 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.
authors.affiliation: Innsbruck Medical University, Clinical Division of Nephrology, Innsbruck, Austria.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Hochegger
authors.forename: Frank
authors.initials: F
authors.lastname: Siebenhaar
authors.forename: Volker
authors.initials: V
authors.lastname: Vielhauer
authors.forename: Dorothea
authors.initials: D
authors.lastname: Heininger
authors.forename: Tanya N
authors.initials: TN
authors.lastname: Mayadas
authors.forename: Gert
authors.initials: G
authors.lastname: Mayer
authors.forename: Marcus
authors.initials: M
authors.lastname: Maurer
authors.forename: Alexander R
authors.initials: AR
authors.lastname: Rosenkranz
mesh_terms: 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
chemical_list: 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