RENAL EPITHELIAL-CELLS RAPIDLY BIND AND INTERNALIZE CALCIUM-OXALATE MONOHYDRATE CRYSTALS
RENAL EPITHELIAL-CELLS RAPIDLY BIND AND INTERNALIZE CALCIUM-OXALATE MONOHYDRATE CRYSTALS
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DOI：
10.1073/pnas.91.15.6987
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发表时间：
1994-07-19
影响因子：
11.1
通讯作者：
TOBACK, FG
中科院分区：
文献类型：
--
作者：
LIESKE, JC;SWIFT, H;TOBACK, FG
肾小管液中的钙离子和草酸根离子过饱和，它们可以成核形成一水草酸钙（COM）晶体，这是肾结石中含量最多的成分。然而，新生晶体保留在肾单位中然后生长成肾结石的机制尚不清楚。COM晶体与肾上皮细胞表面的相互作用可能是肾结石的关键起始事件。为了研究这种可能性，我们使用猴肾上皮细胞（BSC-1系）的培养物作为模型系统，发现[C-14]COM晶体在几秒钟内结合到细胞表面。扫描电子显微镜显示，晶体结合第一顶端微绒毛，随后迁移到晶体表面。当通过透射电子显微镜观察时，细胞内晶体位于囊泡内。通过免疫荧光显微镜观察，发现晶体接触部位的F-肌动蛋白浓度以及含有细胞角蛋白8的中间丝网络的广义重组，寻求对晶体吸收的细胞骨架反应。COM晶体的摄取并没有对肾上皮细胞的生长产生不利影响，并且内化的晶体在分裂过程中明显分布到子细胞中。COM晶体快速粘附于肾小管上皮细胞的顶面，可促进晶体在肾脏中的滞留。阐明调节这一过程的因素可能有助于深入了解肾结石的发病机制。
Renal tubular fluid is supersaturated with calcium and oxalate ions, which can nucleate to form crystals of calcium oxalate monohydrate (COM), the most abundant constituent of kidney stones. However, the mechanisms by which nascent crystals are retained in the nephron and then grow into kidney stones are unclear. An interaction of COM crystals with the surface of renal epithelial cells could be a critical initiating event in nephrolithiasis. To investigate this possibility we used cultures of monkey kidney epithelial cells (BSC-1 line) as a model system and found that [C-14]COM crystals bound to the cell surface within seconds. Scanning electron microscopy revealed that crystals bind first to apical microvilli, which subsequently migrate over the crystalline surface. When visualized by transmission electron microscopy, intracellular crystals were located within vesicles. Cytoskeletal responses to crystal uptake were sought by immunofluorescence microscopy, which revealed concentration of F-actin at sites of crystal Contact as well as a generalized reorganization of the intermediate filament network containing cytokeratin 8. Uptake of COM crystals did not adversely affect renal epithelial cell growth, and internalized crystals were apparently distributed to daughter cells during division. Rapid adherence of COM crystals to the apical surface of tubular epithelial cells could promote crystal retention in the kidney. Elucidation of factors that regulate this process may provide insight into the pathogenesis of nephrolithiasis.