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(The FASEB Journal. 2008;22:lb446)
© 2008 FASEB
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lb446

Mouse Mast Cell Protease 4 has a detrimental role in anti-GBM-induced glomerulonephritis

Lisa Scandiuzzi1,2, Magnus Abrink4, Eric Daugas1,2, Michel Peuchmaur3,5, Renato Monteiro1,2, Gunnar Pejler6 and Ulrich Blank1,2

1 Inserm U699, Paris, France,
2 Faculté de Médecine site Bichat, Université Paris 7, Paris, France,
3 Université Paris 7, Paris, France,
4 Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden,
5 Service de Pathologie, Hôpital Robert Debré, APHP, EA 3102, Paris, France,
6 Dept of Veterinary Medical Chemistry, Swedish University of Agricultural Sciences, Uppsala, Sweden

ABSTRACT

Mast cells (MC) have a protective role in experimental glomerulonephritis (GN). One mechanism could involve release of MC-specific proteases such as chymases mainly expressed in serosal-type MC. Chymase generates pro-inflammatory angiotensin II and is implicated in certain pathophysiological conditions, e.g. angiogenesis, heart failure and fibrosis. We have analysed the role of mouse mast cell protease 4 (mMCP-4), the counterpart of human chymase, in experimental anti-glomerular basement membrane Ab-induced GN. We found that mMCP-4–/– mice have attenuated renal disease as evaluated by blood urea nitrogen and creatinine levels. Histological analysis confirmed that mMCP-4–/– mice have less sub-endothelial deposits and type I collagen. Moreover, mMCP-4–/– mice showed reduced T cell/macrophage infiltration and decreased local IL-6 and MCP-1 mRNA levels. Our results indicate that mMCP-4 has a detrimental role by promoting inflammation. This may at least in part be due to the chemotactic activity of mMCP-4 towards macrophages as shown in an in vitro chemotaxis assay. In conclusion, our results indicate that mMCP-4 does not account for protective function of MCs in renal diseases but rather aggravates disease by enhancing the inflammatory state.





This Article
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