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Crystal Retention Capacity of Cells in the Human Nephron: Involvement of CD44 and Its Ligands Hyaluronic Acid and Osteopontin in the Transition of a Crystal Binding- into a Nonadherent Epithelium

Anja Verhulst^*, Marino Asselman, Veerle P. Persy^*, Marieke S.J. Schepers, Mark F. Helbert^*, Carl F. Verkoelen and Marc E. De Broe^*

*Department of Nephrology-Hypertension, University of Antwerp, Antwerp, Belgium; and Department of Experimental Urology, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands.

Correspondence to Dr. Marc E. De Broe, University of Antwerp, Department of Nephrology-Hypertension, p/a University Hospital Antwerp, Wilrijkstraat 10, B-2650 Edegem/Antwerpen, Belgium. Phone: +32-3-821-3421; Fax: +32-3-829-0100;

ABSTRACT. Nephrolithiasis requires formation of crystals followed by their retention and accumulation in the kidney. Crystal retention can be caused by the association of crystals with the epithelial cells lining the renal tubules. The present study investigated the interaction between calcium oxalate monohydrate (COM) crystals and primary cultures of human proximal (PTC) and distal tubular/collecting duct cells (DTC). Both PTC and DTC were susceptible to crystal binding during the first days post-seeding (4.9 ± 0.8 µg COM/cm²), but DTC lost this affinity when the cultures developed into confluent monolayers with functional tight junctions (0.05 ± 0.02 µg COM/cm²). Confocal microscopy demonstrated the expression of the transmembrane receptor protein CD44 and its ligands osteopontin (OPN) and hyaluronic acid (HA) at the apical membrane of proliferating tubular cells; at confluence, CD44 was expressed at the basolateral membrane and OPN and HA were no longer detectable. In addition, a particle exclusion technique revealed that proliferating cells were surrounded by HA-rich pericellular matrices or "cell coats" extending several microns from the cell surface. Disintegration of these coats with hyaluronidase significantly decreased the cell surface affinity for crystals. Furthermore, CD44, OPN, and HA were also expressed in vivo at the luminal side of tubular cells in damaged kidneys. These results suggest (1) that the intact distal tubular epithelium of the human kidney does not bind crystals, and (2) that crystal retention in the human kidney may depend on the expression of CD44-, OPN-, and-HA rich cell coats by damaged distal tubular epithelium.

E-mail: debroe@uia.ua.ac.be

This article has been cited by other articles:

				C. F. Verkoelen Crystal Retention in Renal Stone Disease: A Crucial Role for the Glycosaminoglycan Hyaluronan? J. Am. Soc. Nephrol., June 1, 2006; 17(6): 1673 - 1687. [Abstract] [Full Text] [PDF]

				M. Asselman, A. Verhulst, M. E. de Broe, and C. F. Verkoelen Calcium Oxalate Crystal Adherence to Hyaluronan-, Osteopontin-, and CD44-Expressing Injured/Regenerating Tubular Epithelial Cells in Rat Kidneys J. Am. Soc. Nephrol., December 1, 2003; 14(12): 3155 - 3166. [Abstract] [Full Text] [PDF]

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