Aluminum-induced alteration of surface anionic sites in cultured brain microvascular endothelial cells

Confluent monolayers of cultured microvascular endothelial cells from goat brain were used as an in vitro model system of the blood-brain barrier to study the effect of aluminum on the anionic sites located on the cell surface. Four experimental groups were used: (1) untreated (control 1) cells growing in normal medium; (2) cells growing in a medium containing 50 M maltol (control 2); (3) cells growing in a medium containing 50 M aluminum maltolate; and (4) cells growing in a medium containing 6 M cadmium chloride as a known cytotoxic substance. The cell cultures were exposed to the substances listed above for 4 days. The anionic sites were detected at the ultrastructural level with cationic colloidal gold and cationized ferritin in non-fixed and fixed cells (prefixation and postfixation procedures). In the applied experimental conditions, aluminum maltolate was found to affect the surface density of anionic sites, as manifested by their redistribution and segmental disappearance from the apical plasmalemma of the endothelial cells. These changes were more pronounced in the non-fixed than the fixed cells and are reversible. Most probably, aluminum, because of its unique properties as a cross-linker, facilitates the lateral migration of anionic sites induced by cationic probes. Whether these alterations contribute to in vivo aluminum-induced blood-brain barrier dysfunction requires further elucidation.Supported in part by funds from the New York State Office of Mental Retardation and Developmental Disabilities and the fund for the Center for Trace Metal Studies and Environmental Neurotoxicology