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


CONCLUSIONS
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.
Rops
Angelique L
AL
Nephrology Research Laboratory, Division of Nephrology, Department of Matrix Biochemistry, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Geert Grooteplein 26-28, 6525 GA Nijmegen, The Netherlands.
van den Hoven
Mabel J
MJ
Bakker
Marinka A
MA
Lensen
Joost F
JF
Wijnhoven
Tessa J
TJ
van den Heuvel
Lambert P
LP
van Kuppevelt
Toin H
TH
van der Vlag
Johan
J
Berden
Jo H
JH
D000328:Adult; D000419:Albuminuria / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001485:Basement Membrane / Q000187:drug effects / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005455:Fluorescent Antibody Technique; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology; D006497:Heparan Sulfate / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007136:Immunoglobulins / Q000187:drug effects / Q000378:metabolism; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000150:complications; D008181:Lupus Nephritis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D019463:Mice, Inbred MRL lpr; D013194:Staining and Labeling; D014018:Tissue Distribution
D006495:Heparin, Low-Molecular-Weight; D006497:Heparan Sulfate; D007136:Immunoglobulins