Adhesion of calcium oxalate monohydrate crystals to renal epithelial cells is inhibited by specific anions.
Adhesion of urinary crystals to the apical surface of renal tubular cells could be a critical step in the formation of kidney stones. The interaction between renal epithelial cells (BSC-1 line) and the most common crystal in kidney stones, calcium oxalate monohydrate (COM), was studied in a tissue culture model system. COM crystals bound to the cell surface within seconds in a concentration-dependent manner to a far greater extent than did brushite, another calcium-containing crystal found in urine. Adhesion of COM crystals to cells was blocked by the polyanion, heparin. Other glycosaminoglycans including chondroitin sulfate A or B, heparan sulfate, and hyaluronic acid, but not chondroitin sulfate C, prevented binding of COM crystals. Two nonsulfated polyanions, polyglutamic acid and polyaspartic acid, also blocked adherence of COM crystals. Three molecules found in urine, nephrocalcin, uropontin, and citrate, each inhibited binding of COM crystals, whereas Tamm-Horsfall glycoprotein (THP) did not. Prior exposure of crystals but not cells to inhibitory molecules blocked adhesion, suggesting that these agents exert their effect at the crystal surface. Inhibition of crystal binding followed a linear Langmuir adsorption isotherm for each inhibitor identified, suggesting that these molecules bind to a single class of sites on the crystal that are important for adhesion to the cell surface. Inhibition of crystal adhesion by heparin was rapidly overcome by the polycation protamine, suggesting that the glycosaminoglycan regulates cell-crystal interactions in a potentially reversible manner.(ABSTRACT TRUNCATED AT 250 WORDS)
Lieske
J C
JC
Department of Medicine, University of Chicago, Illinois 60637, USA.
Leonard
R
R
Toback
F G
FG
D000818:Animals; D000838:Anions / Q000494:pharmacology*; D002129:Calcium Oxalate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002130:Calcium Phosphates / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D002522:Chlorocebus aethiops; D003460:Crystallization; D004285:Dogs; D004847:Epithelial Cells; D004848:Epithelium / Q000502:physiology; D005347:Fibroblasts / Q000502:physiology; D006023:Glycoproteins / Q000494:pharmacology; D006493:Heparin / Q000494:pharmacology; D007668:Kidney / Q000166:cytology / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D053495:Osteopontin; D011506:Proteins / Q000494:pharmacology
D000838:Anions; D002130:Calcium Phosphates; D006023:Glycoproteins; D011506:Proteins; C485828:alpha-tricalcium phosphate; C029490:nephrocalcin; C485830:tetracalcium phosphate; D053495:Osteopontin; D002129:Calcium Oxalate; C485838:calcium phosphate, monobasic, anhydrous; D006493:Heparin; C020243:calcium phosphate; C485829:calcium phosphate, dibasic, anhydrous