SURFACE EXPOSURE OF PHOSPHATIDYLSERINE INCREASES CALCIUM-OXALATE CRYSTAL ATTACHMENT TO IMCD CELLS

The development of urolithiasis is a multifaceted process,starting at urine supersaturation and ending with the formation of mature renal ca lculi. The retention of microcrystals by the urothelial cell membrane is a critical event in the process. The current study examines calcium oxalate monohydrate (COM) crystal attachment to inner medullary colle cting duct (IMCD) cells following selective changes in cell membrane p hospholipid composition. Both primary culture of IMCD cells and a cont inuous IMCD cell line were used for these studies. Cell membrane compo sition was selectively altered by either exogenous addition of membran e phospholipids or using membrane lipid scrambling agents. Enrichment with anionic phospholipids was found to greatly increase attachment of crystals to the cells. This increased attachment correlated with the exposure of phosphatidylserine (PS) on the exofacial leaflet of the ce ll membrane as demonstrated by the use of the membrane scrambling agen t A-23187. Furthermore, the increased COM attachment following PS expo sure could be blocked by incubating the cells with the PS-specific bin ding protein, annexin V. These results support the hypothesis that exp osure of PS head groups on the papillary epithelial cell surface may m ediate stone crystal attachment to the kidney tubule cell epithelium i n the renal papilla, possibly as an initiating event in urolithiasis.