Interaction of glycated albumin-gold complexes with mouse brain microvascular endothelium.
The main objective of this study was to obtain new information about the structural aspects of the enhanced brain uptake of blood-borne glycated albumin observed recently by authors using quantitative, biochemical methodology. Bovine serum albumin glycated in vitro by progressive accumulation of advanced glycosylation end products complexed with colloidal gold (AGE-BSA-G) was used. Mice received a bolus injection of this complex into the common carotid artery and were killed after 3, 15, and 30 minutes. The samples of brain, heart muscles, and liver were processed for transmission electron microscopy. Control mice received injections of native BSA-G complexes. The results indicate the following. (1) Glycation of albumin molecules results in enhanced binding of AGE-BSA-G complexes to the luminal surface of brain microvascular endothelium, which is most pronounced at the earliest times (3 minutes). At later time points, the concentration of circulating complexes decreases rapidly, and some adsorbed particles are endocytosed and internalized in endosomes or multivesicular bodies. Only a few gold particles were found (at 15 minutes) in perivascular neuropil, suggesting their negligible transvascular passage. (2) Presumably as a result of the competition of blood plasma albumin, BSA-G complexes were almost not adsorbed or internalized. (3) Circulating AGE-BSA-G complexes were phagocytosed rapidly in liver sinusoids, mainly by reticulo-endothelial cells. They also were endocytosed and transcytosed by heart capillary endothelia and by fenestrated endothelia of the brain circumventricular organs. The binding of AGE-BSA-G complexes suggests the presence of receptors for AGE on the surface of the brain microvascular endothelium. However, the presence of these receptors presumably is not sufficient for making the blood-brain barrier fully permeable for circulating complexes.
Vorbrodt
A W
AW
New York State Office of Mental Retardation and Developmental Disabilities, Institute for Basic Research in Developmental Disabilities, Staten Island 10314, USA.
Dobrogowska
D H
DH
D000818:Animals; D001812:Blood-Brain Barrier; D001921:Brain / Q000098:blood supply*; D002199:Capillary Permeability; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000648:ultrastructure; D005260:Female; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D017979:Gold Colloid / Q000032:analysis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008833:Microcirculation; D008854:Microscopy, Electron; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000378:metabolism*
D017127:Glycation End Products, Advanced; D017979:Gold Colloid; D011956:Receptors, Cell Surface; D012710:Serum Albumin, Bovine