title: Endocytosis of advanced glycation end-products in bovine choriocapillaris endothelial cells.
abstract: OBJECTIVE
  Age-related changes in Bruch's membrane (BM), situated between the retina and the choroid, include the accumulation of advanced glycation end-products (AGEs) and other modified macromolecules. An important clearance mechanism for such molecules is endocytosis via macrophages and specialized endothelial cells. This study examined the endocytic clearance of AGEs in choriocapillaris endothelial (CCE) cells, which are strategically located beneath the BM.
  
  
  METHODS
  Bovine CCE cultures were incubated with radiolabeled or fluorescently labeled AGE-modified bovine serum albumin (AGE-BSA). Cells and tissues were examined for the expression of two AGE-binding scavenger receptors, stabilin-1 and -2, by immunohistochemistry and Western blotting, and with antibody inhibition studies.
  
  
  RESULTS
  CCE cells effectively endocytosed AGE-BSA via a scavenger receptor-mediated pathway. A polyclonal antibody against stabilin-2 significantly inhibited endocytosis (40%). Tissue sections stained positive for stabilin-2 and -1 in the choriocapillaris layer, which was confirmed by immunoblots of cell extracts. Colocalization of stabilin-1 and -2 and internalized AGE-BSA was seen in early endosomes.
  
  
  CONCLUSIONS
  CCEs actively endocytose AGE-BSA and express the scavenger receptors, stabilin-1 and -2, of which at least stabilin-2 is involved in AGE-BSA uptake. Impairment of this stabilin-mediated clearance function may contribute to depositions of waste macromolecules in BM and subsequent retinopathy.
authors: Department of Cell Biology and Histology, Institute of Medical Biology, University of Tromsø, Norway. ruomei.li@uit.no
authors: Ruomei
authors: R
authors: Li
authors: Peter
authors: P
authors: McCourt
authors: Kai
authors: K
authors: Schledzewski
authors: Sergij
authors: S
authors: Goerdt
authors: Gerhard
authors: G
authors: Moldenhauer
authors: Xipu
authors: X
authors: Liu
authors: Bård
authors: B
authors: Smedsrød
authors: Karen Kristine
authors: KK
authors: Sørensen
mesh_terms: D000818:Animals; D016570:Bruch Membrane; D002196:Capillaries / Q000166:cytology; D002417:Cattle; D015816:Cell Adhesion Molecules, Neuronal / Q000032:analysis; D002478:Cells, Cultured; D002829:Choroid / Q000098:blood supply; D004705:Endocytosis; D042783:Endothelial Cells / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology*; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D051116:Receptors, Scavenger / Q000032:analysis
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D017127:Glycation End Products, Advanced; D051116:Receptors, Scavenger