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NDT Advance Access originally published online on June 5, 2007
Nephrology Dialysis Transplantation 2007 22(7):1891-1902; doi:10.1093/ndt/gfm194
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© The Author [2007]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Expression of glomerular heparan sulphate domains in murine and human lupus nephritis

Angelique L. Rops1, Mabel J. van den Hoven1, Marinka A. Bakker1, Joost F. Lensen2, Tessa J. Wijnhoven2,3, Lambert P. van den Heuvel3, Toin H. van Kuppevelt2, Johan van der Vlag1 and Jo H. Berden1

1Nephrology Research Laboratory, Division of Nephrology, 2Department of Matrix Biochemistry, Nijmegen Centre for Molecular Life Sciences and 3Department of Pediatrics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

Correspondence and offprint requests to: Jo H. Berden, MD PhD, Nephrology Research Laboratory, Division of Nephrology (464), Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Geert Grooteplein 26-28, 6525 GA Nijmegen, The Netherlands. Email: j.berden{at}nier.umcn.nl



  Abstract

Background. Recently, we identified specific N- and 6-O-sulphated heparan sulphate (HS) domains on activated glomerular endothelial cells. In this study, we evaluated in lupus nephritis the expression of different HS domains on glomerular endothelium and in the glomerular basement membrane (GBM).

Methods. The expression of specific glomerular HS domains and the presence of immunoglobulins (Ig) were determined by immunofluorescence staining of kidney sections of patients with nephritis due to systemic lupus erythematosus (SLE) and MRL/lpr lupus mice. The expression/presence of glomerular HS domains and Ig was also evaluated after eluting Ig from renal sections of lupus mice using two elution methods, and in renal sections of lupus mice treated with heparinoids.

Results. Both MRL/lpr mice and patients with lupus nephritis showed a decreased expression of HS in the GBM. The expression of N- and 6-O-sulphated HS domains on glomerular endothelium was decreased in MRL/lpr mice, but increased in SLE patients. MRL/lpr mice had more extensive glomerular Ig deposits than SLE patients. After elution of Ig, the glomerular endothelial expression of N- and 6-O-sulphated HS domains in MRL/lpr mice was recovered and even increased above normal levels, while the expression of HS in the GBM was restored to normal levels. Treatment with heparinoids prevented Ig deposition and preserved the expression of glomerular HS domains at normal levels in lupus mice.

Conclusion. The expression of specific HS domains on glomerular endothelium and in the GBM is changed during lupus nephritis due to masking by Ig deposits and induction of inflammatory N- and 6-O-sulphated HS domains.

Keywords: albuminuria; glomerular basement membrane; glomerular endothelial cells; glomerulonephritis; heparan sulphate; heparinoids; systemic lupus erythematosus

Received for publication: 30.10.06
Accepted in revised form: 13. 3.07


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Expression of glomerular heparan sulphate domains in murine and human lupus nephritis
Angelique L. Rops, Mabel J. van den Hoven, Marinka A. Bakker, Joost F. Lensen, Tessa J. Wijnhoven, Lambert P. van den Heuvel, Toin H. van Kuppevelt, Johan van der Vlag, and Jo H. Berden
NDT 2007 22: 2416. [Extract] [FREE Full Text]  





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