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R. Li, P. McCourt, K. Schledzewski, S. Goerdt, X. Liu, B. Smedsrød, K. Sørensen; Expression of Stabilins in Bovine Choriocapillary Endothelial Cells . Invest. Ophthalmol. Vis. Sci. 2006;47(13):4153.
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Two new scavenger receptors, stabilin–1 and stabilin–2, have been recently identified (McCourt et al. 1999; Politz et al. 2002), and reported to mediate endocytosis of various physiological and pathophysiological substances including connective tissue macromolecules and advanced glycation end products (AGEs), which accumulated in vascular tissue in ageing and diabetes. Age–related retinal disease correlates with changes in Bruch’s membrane, which also include accumulation of AGEs and other modified macromolecules.
The stabilins are mainly expressed in endocytically active endothelia in liver, bone marrow and lymph nodes. Both receptors bind AGE–modified albumin, and stabilin–2 is reported to be the major receptor responsible for uptake of AGEs in the liver sinusoidal endothelial cells (Hansen et al. 2002), which are the major scavenger cells for soluble macromolecular waste material in the blood. We have found that long–term cultures of bovine choriocapillaris endothelial cells (CCE) also show effective endocytosis of AGE–modified albumin (bovine; AGE–BSA). Our hypothesis is that CCE, being located closely to the Bruch’s membrane, exerts a local scavenger function, and that changes in this cell layer leading to reduced endocytosis may be associated with accumulation of AGEs in Bruch's membrane.
The aim of the study was to examine expression of stabilins in CCE.
Long–term cultures of bovine CCE were established as described (Liu & Li 1993), and frozen sections of bovine retinal pigment epithelial cells (RPE) and choroid were prepared. Cultured CCE were CD31 and vWf positive. Immunocytochemistry and western blot analysis were done using polyclonal antibodies raised against mouse, rat and human stabilin–1 and –2. Endocytosis of radiolabelled AGE–BSA co–incubated with a rabbit anti–rat stabilin–2 antibody, or rabbit non–immune IgG, was examined.
Cultured CCE stained positive for stabilin–1 and –2. The expression of both stabilins was confirmed in CCE by western blotting. Immunohistochemistry of choroid/RPE sections showed positive staining of endothelial cells of the choriocapillaris and larger choroid vessels. Endocytosis of AGE–BSA in CCE cultures was significantly inhibited by co–incubation with stabilin–2 antibody in a dose–dependent manner.
We conclude that bovine CCE express stabilin–1 and –2 receptors, and that stabilin–2 may be partly responsible for the uptake of AGE–BSA.
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