ADHESION OF CALCIUM-OXALATE MONOHYDRATE CRYSTALS TO RENAL EPITHELIAL-CELLS IS INHIBITED BY SPECIFIC ANIONS
ADHESION OF CALCIUM-OXALATE MONOHYDRATE CRYSTALS TO RENAL EPITHELIAL-CELLS IS INHIBITED BY SPECIFIC ANIONS
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DOI：
10.1152/ajprenal.1995.268.4.f604
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发表时间：
1995-04-01
期刊：
影响因子：
--
通讯作者：
TOBACK, FG
中科院分区：
文献类型：
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作者：
LIESKE, JC;LEONARD, R;TOBACK, FG
尿晶体附着在肾小管细胞的顶端表面可能是肾结石形成的关键步骤。在组织培养模型系统中，研究了肾上皮细胞（BSC-1系）与肾结石中最常见的晶体草酸钙（COM）的相互作用。COM晶体在几秒钟内以浓度依赖的方式结合到细胞表面，其程度远远大于尿中发现的另一种含钙晶体刷石。COM晶体与细胞的粘附被聚阴离子肝素阻断。其他糖胺聚糖包括硫酸软骨素A或B、硫酸肝素和透明质酸，但不包括硫酸软骨素C，可以阻止COM晶体的结合。两种非硫酸盐化的聚阴离子，聚谷氨酸和聚天冬氨酸，也阻断了COM晶体的粘附。尿中发现的三种分子，肾钙素、尿桥蛋白和柠檬酸盐，都能抑制COM晶体的结合，而Tamm-Horsfall糖蛋白（THP）则没有。事先将晶体而不是细胞暴露在抑制分子中会阻止粘附，这表明这些物质在晶体表面发挥作用。每种抑制剂对晶体结合的抑制都遵循线性Langmuir吸附等温线，这表明这些分子与晶体上的一类位点结合，这些位点对细胞表面的粘附很重要。肝素对晶体粘附的抑制作用被多阳离子鱼精蛋白迅速克服，这表明糖胺聚糖以一种潜在可逆的方式调节细胞-晶体相互作用。因此，COM晶体在肾细胞表面的快速粘附可被尿中发现的各种阴离子（糖胺聚糖、尿桥蛋白、肾钙素、柠檬酸盐）阻断，但并非所有阴离子都具有这种特性（THP、白蛋白）。晶体保留和随后形成的肾结石可能是由尿阴离子的结构、功能或数量的改变介导的。
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. Thus rapid adhesion of COM crystals to the renal cell surface can be blocked by diverse anions found in urine (glycosaminoglycans, uropontin, nephrocalcin, citrate), but not all share this property (THP, albumin). Crystal retention and the subsequent formation of a renal calculus could be mediated by alterations in the structure, function, or quantity of urinary anions.