TY - JOUR
T1 - Sialic acid-containing glycoproteins on renal cells determine nucleation of calcium oxalate dihydrate crystals
AU - Lieske, John C.
AU - Toback, F. Gary
AU - Deganello, Sergio
N1 - Funding Information:
This work was supported by grants from the National Institutes of Health (Clinical Investigator Award K08 DK 02272, R01 DK 53399) and the Oxalosis and Hyperoxaluria Foundation to J.C.L.; O'Brien Kidney Research Center P50 DK 47631 to J.C.L. and F.G.T.; and C.N.R grant 1169 to S.D. We thank E. Williamson of the University of Chicago Cancer Research Center Electron Microscopy Core and J. Charlesworth of the Mayo Clinic Electron Microscopy Core Facility, as well as G. Farell-Baril and E. Huang for excellent technical assistance. We also thank J.G. Kleinman and A. Beshensky, Medical College of Wisconsin, Milwaukee, WI, USA, for supplying the cIMCD cells used in this study.
PY - 2001
Y1 - 2001
N2 - Background. The interaction between the surfaces of renal epithelial cells and calcium oxalate dihydrate (COD), the most common crystal in human urine, was studied to identify critical determinants of kidney stone formation. Methods. A novel technique utilizing vapor diffusion of oxalic acid was employed to nucleate COD crystals onto the apical surface of living cells. Confluent monolayers were grown in the inner 4 wells of 24-well culture plates. To identify cell surface molecules that regulate crystal nucleation, cells were pretreated with a protease (trypsin or proteinase K) to alter cell surface proteins, neuraminidase to alter cell surface sialoglycoconjugates, or buffer alone. COD crystals were nucleated on the surface of cells by diffusion of oxalic acid vapor into a calcium-containing buffer overlying the cells. Crystal face-specific nucleation was evaluated by scanning electron microscopy. Results. Nucleation and growth of a COD crystal onto an untreated control cell occurred almost exclusively via its (001) face, an event rarely observed during COD crystallization. In contrast, when COD crystals were nucleated onto protease- or neuraminidase-treated cells, they did so via the (100) face of the crystal. Conclusions. Specific sialic acid-containing glycoproteins, and possibly glycolipids (sialoglycoconjugates), appear to be critical determinants of face-specific nucleation of COD crystals on the apical renal cell surface. We hypothesize that crystal retention within the nephron, and the subsequent development of a kidney stone, may result when the number or composition of these cell surface molecules is modified by genetic alterations, cell injury, or drugs in tubular fluid.
AB - Background. The interaction between the surfaces of renal epithelial cells and calcium oxalate dihydrate (COD), the most common crystal in human urine, was studied to identify critical determinants of kidney stone formation. Methods. A novel technique utilizing vapor diffusion of oxalic acid was employed to nucleate COD crystals onto the apical surface of living cells. Confluent monolayers were grown in the inner 4 wells of 24-well culture plates. To identify cell surface molecules that regulate crystal nucleation, cells were pretreated with a protease (trypsin or proteinase K) to alter cell surface proteins, neuraminidase to alter cell surface sialoglycoconjugates, or buffer alone. COD crystals were nucleated on the surface of cells by diffusion of oxalic acid vapor into a calcium-containing buffer overlying the cells. Crystal face-specific nucleation was evaluated by scanning electron microscopy. Results. Nucleation and growth of a COD crystal onto an untreated control cell occurred almost exclusively via its (001) face, an event rarely observed during COD crystallization. In contrast, when COD crystals were nucleated onto protease- or neuraminidase-treated cells, they did so via the (100) face of the crystal. Conclusions. Specific sialic acid-containing glycoproteins, and possibly glycolipids (sialoglycoconjugates), appear to be critical determinants of face-specific nucleation of COD crystals on the apical renal cell surface. We hypothesize that crystal retention within the nephron, and the subsequent development of a kidney stone, may result when the number or composition of these cell surface molecules is modified by genetic alterations, cell injury, or drugs in tubular fluid.
KW - Cell membrane
KW - Crystallization
KW - Kidney calculi
KW - Neuraminidase
KW - Protease
KW - Renal stones
KW - Sialoglycoconjugates
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U2 - 10.1046/j.1523-1755.2001.00015.x
DO - 10.1046/j.1523-1755.2001.00015.x
M3 - Article
C2 - 11703596
AN - SCOPUS:0034783849
SN - 0085-2538
VL - 60
SP - 1784
EP - 1791
JO - Kidney international
JF - Kidney international
IS - 5
ER -