Basolateral Aggregated Rat Amyloidβ(1-42) Potentiates Transmigration of Primary Rat Monocytes through a Rat Blood-Brain Barrier

Abstract

Monocytes adhere and transmigrate through a blood-brain barrier (BBB) during a normal immune patrol and after pathological events. It is well established that the transmigration of monocytes through the BBB is stimulated by soluble amyloidbeta. The aim of the present study was to explore if aggregated amyloidbeta added to the basolateral side of a BBB may modulate the adhesion and migration of primary rat monocytes through a monolayer of rat brain capillary endothelial cells (BCEC). Monocytes were freshly isolated from rat blood by negative magnetic selection and applied to the apical side of a fully confluent BCEC-monolayer with or without pre-treatment with soluble or aggregated amyloidbeta. Aggregation was performed by incubation of amyloidbeta(1-42) for 2 weeks in acidic medium at 37 degrees C. The monocytes adhered at the apical side of a BCEC-monolayer within 30-90 min (approx. 1,500 cells/well), and transmigrated to the basolateral side within 18 hours (approx. 40,000 cells/well), when stimulated with 1 ng/ml monocyte chemotactic protein-1. Soluble amyloidbeta(1-42) (100 ng/ml) significantly enhanced the adhesion and migration of monocytes after 90 min, which was modulated by antibodies against platelet-endothelial cell adhesion molecule-1, intracellular adhesion molecule-1, receptor for advanced glycosylation end products and low density lipoprotein-related protein-1 but not vascular cell adhesion molecule-1. Addition of aggregated amyloidbeta(1-42) to the basolateral side potentiated the transmigration of monocytes. In conclusion, aggregated amyloidbeta(1-42) stimulates the transmigration of monocytes through a BBB, which is of importance in Alzheimers disease.