Bigelow M W, Wiessner J H, Kleinman J G, Mandel N S
Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin 53295, USA.
Calcif Tissue Int. 1997 Apr;60(4):375-9. doi: 10.1007/s002239900246.
The development of urolithiasis is a multifaceted process, starting with urine supersaturation and ending with the formation of mature renal calculi. The retention of microcrystals by kidney tubule epithelium cell membranes has been proposed as a critical event in the process. To date, attachment of kidney stone constituent crystals to urothelial cells has been demonstrated both in vitro and in vivo yet the mechanism of crystal attachment remains unknown. We hypothesize that for effective stone crystal attachment to the epithelium there must be cell membrane rearrangement that would allow for long-range bonding between the stone crystal and the cell membrane. This rearrangement may be influenced by the physical state of the membrane. The current study examines calcium oxalate monohydrate (COM) crystal attachment to inner medullary collecting duct (IMCD) cells following changes in cell membrane fluidity. Radioactively labeled COM crystals were used to quantitate crystal attachment. Membrane fluidity was altered by changing temperature, cell membrane cholesterol content, or extended length of cell culture. Crystal attachment to IMCD cells was directly correlated to changes in membrane fluidity. This finding was consistently observed regardless of the method used to alter membrane fluidity. The results are consistent with the theory that the ability to form a crystal attachment region on the cell surface may be related to the ease of rearrangement of membrane components at the cell surface. Variations in the urothelial cell environment during certain pathological conditions in the kidney could induce these physical perturbations and prime kidney epithelial cells at or near the papillary tip to bind COM crystals.
尿石症的发展是一个多方面的过程，始于尿液过饱和，终于成熟肾结石的形成。肾小管上皮细胞膜对微晶的滞留被认为是该过程中的一个关键事件。迄今为止，肾结石成分晶体与尿路上皮细胞的附着在体外和体内均已得到证实，但晶体附着的机制仍不清楚。我们假设，为了使结石晶体有效地附着于上皮细胞，细胞膜必须发生重排，从而使结石晶体与细胞膜之间形成远距离结合。这种重排可能受膜的物理状态影响。本研究检测了细胞膜流动性改变后一水草酸钙（COM）晶体与髓质内层集合管（IMCD）细胞的附着情况。用放射性标记的COM晶体来定量晶体附着。通过改变温度、细胞膜胆固醇含量或延长细胞培养时间来改变膜流动性。COM晶体与IMCD细胞的附着与膜流动性的变化直接相关。无论采用何种方法改变膜流动性，均一致观察到这一结果。这些结果与以下理论一致，即细胞表面形成晶体附着区域的能力可能与细胞表面膜成分重排的难易程度有关。肾脏某些病理状态下尿路上皮细胞环境的变化可能会引发这些物理扰动，并使乳头尖端或其附近的肾上皮细胞易于结合COM晶体。
