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Glomerular Endothelial Glycocalyx Constitutes a Barrier to Protein Permeability

Anurag Singh^*, Simon C. Satchell^*, Chris R. Neal, Edward A. McKenzie, John E. Tooke and Peter W. Mathieson^*

^* Academic Renal Unit, Southmead Hospital; Microvascular Research Laboratories, University of Bristol; Faculty of Life Sciences, Michael Smith Building, University of Manchester, Manchester; and Department of Vascular Medicine and Diabetes Research, Peninsula Medical School, University of Exeter, Exeter, United Kingdom

Correspondence: Dr. Anurag Singh, Academic Renal Unit, Paul O'Gorman Lifeline Centre, Clinical Sciences at North Bristol, University of Bristol, Southmead Hospital, Bristol, BS10 5NB, UK. Phone/Fax: +44-117-959-5438; E-mail: Anurag.Singh{at}bristol.ac.uk

Received for publication January 28, 2007. Accepted for publication June 18, 2007.

Glycocalyx, composed of glycoproteins including proteoglycans, coats the luminal surface of the glomerular capillaries. Human heparanase degrades heparan sulphate glycosaminoglycans and is up-regulated in proteinuric states. In this study, we analyze the structure of the human glomerular endothelial cell glycocalyx in vitro and examine its functional relevance, especially after treatment with human heparanase. Electron microscopy of conditionally immortalized glomerular endothelial cells revealed a 200-nm thick glycocalyx over the plasma membrane, which was also demonstrated by confocal microscopy. Neuraminidase treatment removed the majority of glycocalyx, reduced trans-endothelial electrical resistance by 59%, and increased albumin flux by 207%. Heparinase III and human heparanase specifically cleaved heparan sulphate: this caused no change in trans-endothelial electrical resistance, but increased the albumin passage across the monolayers by 40% and 39%, respectively. Therefore, we have characterized the glomerular endothelial cell glycocalyx and have shown that it contributes to the barrier to flux of albumin across the cell layer. These results suggest an important role for this glycocalyx in the restriction of glomerular protein passage in vivo and suggest ways in which human heparanase levels may be linked to proteinuria in clinical disease.

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Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673