Surface exposure of phosphatidylserine increases calcium oxalate
crystal attachment to imcd cells.
Bigelow, Michael W., John H. Wiessner, Jack G. Kleinman, and Neil S.
Mandel.
Department of Medicine, Medical College of Wisconsin and Department
of Veterans Affairs Medical Center, Milwaukee, WI 53295
APStracts 3:0174F, 1996.
The development of urolithiasis is a multifaceted process, starting at
urine supersaturation and ending with the formation of mature renal
calculi. 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 collecting duct (IMCD) cells following selective
changes in cell membrane phospholipid composition. Both primary
culture of IMCD cells and a continuous IMCD cell line were used for
these studies. Cell membrane composition was selectively altered by
either exogenous addition of membrane 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 cell membrane
as demonstrated by the use of the membrane scrambling agent A23187.
Furthermore, the increased COM attachment following PS exposure could
be blocked by incubating the cells with the PS-specific binding
protein, annexin V. These results support the hypothesis that
exposure of PS head-groups on the papillary epithelial cell surface
may mediate stone crystal attachment to the kidney tubule cell
epithelium in the renal papilla, possibly as an initiating event in
urolithiasis.
Received 13 May 1996; accepted in final form 24 September 1996.
APS Manuscript Number F146-6.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 5 November 1996