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This Article Full Text Full Text (PDF) All Versions of this Article: 294/1/F253    most recent 00429.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Celie, J. W. A. M. Articles by van den Born, J. Search for Related Content PubMed PubMed Citation Articles by Celie, J. W. A. M. Articles by van den Born, J.

Tubulointerstitial heparan sulfate proteoglycan changes in human renal diseases correlate with leukocyte influx and proteinuria

¹Departments of Molecular Cell Biology and Immunology and ³Nephrology, VU University Medical Center, and ²Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands

Submitted 12 September 2007 ; accepted in final form 16 November 2007

Heparan sulfate proteoglycans (HSPGs) are well known for their proposed role in glomerular filtration. In addition, HSPGs can bind the leukocyte adhesion molecule L-selectin and chemokines, suggesting a role in inflammation. We examined a panel of biopsies representing different human primary kidney diseases for L-selectin and monocyte chemoattractant protein-1 (MCP-1) binding. In various renal diseases, L-selectin and MCP-1 binding to interstitial perivascular matrix HSPGs is increased, which is significantly associated with leukocyte influx. In proteinuric diseases, including membranous glomerulopathy, minimal change disease, but also IgA nephropathy and lupus nephritis, increased binding of L-selectin and MCP-1 to tubular epithelial cell (TEC) HSPGs is observed, which colocalizes with increased basolateral syndecan-1 and anti-heparan sulfate 10E4 staining. Short-hairpin RNA-mediated silencing demonstrates that syndecan-1 on TECs indeed mediates L-Selectin binding. Increased TEC expression of IL-8 in biopsies of proteinuric patients suggests that the increase in luminal protein may activate TECs to increase expression of L-selectin and MCP-1 binding syndecan-1. Strikingly, urinary syndecan-1 from proteinuric patients is less capable of binding L-selectin compared with urinary syndecan-1 from healthy controls, although syndecan-1 concentrations are similar in both groups. Together, our data show pronounced tubulointerstitial HSPG alterations in primary kidney disease, which may affect the inflammatory response.

adhesion molecule; chemokine; tubular epithelial cells; inflammation