Adhesion of calcium oxalate monohydrate crystals to anionic sites on the surface of renal epithelial cells

Lieske, John C.; Leonard, Reid J.; Swift, Hewson; Toback, F. Gary

doi:10.1152/ajprenal.1996.270.1.f192

Cited by 73 publications

(97 citation statements)

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“…However, binding of microcrystals to the apical surface of tubular cells (5,11) or perhaps nucleation on the cell surface (36) followed by cellular processing of the crystals (11,37) could be important determinants of intranephronal calcification. Our study supports the hypothesis that injury of tubular cells favors crystal deposition (33) and possibly promotes kidney stone formation.…”

Section: Discussionmentioning

confidence: 99%

“…One hour later, the buffer was aspirated and replaced with DMEM that contained 5% calf serum. 2 , 0.5 mM MgCl 2 , 5.6 mM glucose) at 38°C as described previously (5). Preliminary experiments defined these enzyme concentrations as having maximal effects on crystal binding without being cytotoxic.…”

Section: Uric Acid and Uric Acid Crystal Treatment Of Monolayersmentioning

confidence: 99%

“…Therefore, we and others have hypothesized that attachment of newly formed crystals to the tubular cell surface (5-10) and the cellular responses that follow (11)(12)(13) could result in crystal retention and thereby set in motion a series of events that lead to pathologic renal calcification. Adhesion of calcium oxalate crystals to anionic, sialic acid-containing molecules on the surface of renal epithelial cells is crystal-face specific (14) and can be blocked by competing soluble anions in tubular fluid such as glycosaminoglycans, citrate, or glycoproteins (5,6). Exposure of cells to agents that raise intracellular cAMP, including prostaglandin E 2 , (PGE 2 ), decreases cellular affinity for crystals, whereas blockade of PGE production enhances it (15).…”

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confidence: 99%

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Modulation of Proliferating Renal Epithelial Cell Affinity for Calcium Oxalate Monohydrate Crystals

Farell¹,

Huang

Kim

et al. 2004

Journal of the American Society of Nephrology

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Abstract. Adhesion of urinary crystals to distal tubular cells could be a critical event that triggers a cascade of responses ending in kidney stone formation. Monolayer cultures of distal nephronderived MDCKI cells were used as a model to study crystal-cell interactions. COM crystal adhesion reached a peak 2 d after plating and progressively fell thereafter. The decline in crystal binding was accelerated by prostaglandin E 2 (PGE 2 ) supplementation and delayed by blockade of PG production. Crystals avidly adhered to cells that migrated in to repair a scrape wound made in the monolayer and after a transient hypoglycemic insult. Exposure of MDCKI cells to uric acid crystals and soluble uric acid was also associated with increased crystal adhesion. Treatment of physically or hypoglycemically injured cells with trypsin or neuraminidase reduced crystal binding to baseline levels, suggesting that increased exposure of cell surface glycoproteins mediated the effect, whereas PGE 2 treatment blunted crystal binding to regenerating cells. Furthermore, when cells were grown in the presence of synthetic D-mannosamine analogues that can modify the conformation of cell surface sialoglycoconjugates, crystal binding to proliferating cells was decreased, whereas blockade of N-

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Section: Discussionmentioning

confidence: 99%

Section: Uric Acid and Uric Acid Crystal Treatment Of Monolayersmentioning

confidence: 99%

mentioning

confidence: 99%

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Modulation of Proliferating Renal Epithelial Cell Affinity for Calcium Oxalate Monohydrate Crystals

Farell¹,

Huang

Kim

et al. 2004

Journal of the American Society of Nephrology

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“…Those studies showed that COM crystals, which are the predominant form of CaOx occurring in human kidney stones (41), are highly membranolytic (55), and also that their adherence to renal epithelial cells is very rapid, concentration dependent, and significantly greater than crystals of other calcium minerals (33, 36 -37). COM crystals were also shown to adhere to anionic sites on the surface of renal epithelial cells (32), while their attachment was altered by manipulating either cell surface characteristics and/or concentrations of soluble proteins and anions in the culture medium (31)(32)(33)54). Furthermore, in cell lines with properties similar to those of proximal tubules, adhesion of crystals was followed by their internalization and subsequent dissolution, which took 5-7 wk (34).…”

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confidence: 99%

Intracrystalline urinary proteins facilitate degradation and dissolution of calcium oxalate crystals in cultured renal cells

Grover¹,

Thurgood²,

Fleming³

et al. 2008

American Journal of Physiology-Renal Physiology

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134: 5-14, 2001. The aim of this investigation was to determine the effect of increasing concentrations of intracrystalline protein on the rate of CaOx crystal dissolution in Madin-Darby canine kidney (MDCKII) cells. Crystal matrix extract (CME) was isolated from urinary CaOx monohydrate (COM) crystals. Cold and [ 14 C]oxalate-labeled COM crystals were precipitated from ultrafiltered urine containing 0 -5 mg/l CME. Crystal surface area was estimated from scanning electron micrographs, and synchrotron X-ray diffraction was used to determine nonuniform strain and crystallite size. Radiolabeled crystals were added to MDCKII cells and crystal dissolution, expressed as radioactive label released into the medium, was measured. Increasing CME content did not significantly alter crystal surface area. However, nonuniform strain increased and crystallite size decreased in a dose-response manner, both reaching saturation at a CME concentration of 3 mg/ and demonstrating unequivocally the inclusion of increasing quantities of proteins in the crystals. This was confirmed by Western blotting. Crystal dissolution also followed saturation kinetics, increasing proportionally with final CME concentration and reaching a plateau at a concentration of ϳ2 mg/l. These findings were complemented by field emission scanning electron microscopy, which showed that crystal degradation also increased relative to CME concentration. Intracrystalline proteins enhance degradation and dissolution of CaOx crystals and thus may constitute a natural defense against urolithiasis. The findings have significant ramifications in biomineral metabolism and pathogenesis of renal stones. nephrocalcinosis; urolithiasis THE PATHOGENESIS OF RENAL calculi requires the sequential combination of two processes, namely, the nucleation of crystals and their retention within the kidney. While crystal nucleation requires supersaturation of urine with calcium oxalate (CaOx), renal crystal trapping has been explained by either the "free particle" or "fixed particle" theory. Although both these theories appear equally plausible (26), current consensus favors a fixed particle mechanism. This view is supported by the results of studies performed in the early 1990s, which demonstrated for the first time that CaOx crystals irreversibly adhere to and are phagocytosed by cultured renal epithelial cells (35,39). These findings introduced a new paradigm to urolithiasis research because they validated the credibility of using this experimental approach to examine and manipulate factors affecting the regulation of crystal retention, which had not previously been possible. Consequently, there followed a series of reports investigating factors affecting interactions between CaOx monohydrate (COM) crystals and renal cells (reviewed in Refs. 30 and 38). Those studies showed that COM crystals, which are the predominant form of CaOx occurring in human kidney stones (41), are highly membranolytic (55), and also that their adherence to renal epithelial cells is very rapid, concentration ...

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“…In addition, it appears mathematically unlikely that nucleation and growth of an individual crystal could produce a particle large enough to occlude a nephron lumen (4). Therefore, our laboratory (5)(6)(7)(8)(9)(10)(11) and others (12)(13)(14)(15)(16)(17) have investigated the mechanism(s) whereby urinary crystals can interact with renal epithelial cells; once adherent to a cell, smaller particles could be retained and serve as a nidus for renal stone formation.…”

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confidence: 99%

Annexin II Is Present on Renal Epithelial Cells and Binds Calcium Oxalate Monohydrate Crystals

Kumar¹,

Farell²,

Deganello³

et al. 2003

Journal of the American Society of Nephrology

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Abstract. Attachment of newly formed crystals to renal epithelial cells appears to be a critical step in the development of kidney stones. The current study was undertaken to identify potential calcium oxalate monohydrate (COM) crystal-binding proteins on the surface of renal tubular cells. Apical membranes were prepared from confluent monolayers of renal epithelial cells (MDCKI line), and COM crystal affinity was used to isolate crystal-binding proteins that were then subjected to electrophoresis and electroblotting. Microsequencing of the most prominent COM crystal-binding protein (M r of 37 kD) identified it as annexin II (Ax-II). When exposed proteins on the surface of intact monolayers were biotinylated and then isolated using streptavidin agarose beads, Ax-II was detected, suggesting that at least a portion is exposed on the apical cell surface. Ax-II was not completely extracted by 0.1 M Na 2 CO 3 , suggesting that at least a portion of cellular Ax-II is an intrinsic membrane-bound protein. Using confocal immunofluorescence microscopy, Ax-II was visualized together with Caveolin-1 (Cav-1) on the apical membrane of intact MDCKI cells. Cells pretreated with a monoclonal anti-Ax-II antibody bound significantly fewer COM crystals, whereas anti-LDL receptor antibody did not decrease COM binding, further suggesting a functional role for Ax-II during adhesion of crystals to intact cells. These results suggest that Ax-II avidly binds COM crystals and is present on the apical surface of MDCKI cells.

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Adhesion of calcium oxalate monohydrate crystals to anionic sites on the surface of renal epithelial cells

Cited by 73 publications

References 0 publications

Modulation of Proliferating Renal Epithelial Cell Affinity for Calcium Oxalate Monohydrate Crystals

Modulation of Proliferating Renal Epithelial Cell Affinity for Calcium Oxalate Monohydrate Crystals

Intracrystalline urinary proteins facilitate degradation and dissolution of calcium oxalate crystals in cultured renal cells

Annexin II Is Present on Renal Epithelial Cells and Binds Calcium Oxalate Monohydrate Crystals

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