R. Giri et al., beta-Amyloid-induced migration of monocytes across human brain endothelialcells involves RAGE and PECAM-1, AM J P-CELL, 279(6), 2000, pp. C1772-C1781
In patients with amyloid beta -related cerebrovascular disorders, e.g., Alz
heimer's disease, one finds increased deposition of amyloid peptide (A beta
) and increased presence of monocyte/microglia cells in the brain. However,
relatively little is known of the role of A beta in the trafficking of mon
ocytes across the blood-brain barrier (BBB). Our studies show that interact
ion of A beta (1-40) with monolayer of human brain endothelial cells result
s in augmented adhesion and transendothelial migration of monocytic cells (
THP-1 and HL-60) and peripheral blood monocytes. The A beta -mediated migra
tion of monocytes was inhibited by antibody to A beta receptor (RAGE) and p
latelet endothelial cell adhesion molecule (PECAM-1). Additionally, A beta
-induced transendothelial migration of monocytes were inhibited by protein
kinase C inhibitor and augmented by phosphatase inhibitor. We conclude that
interaction of A beta with RAGE expressed on brain endothelial cells initi
ates cellular signaling leading to the transendothelial migration of monocy
tes. We suggest that increased diapedesis of monocytes across the BBB in re
sponse to A beta present either in the peripheral circulation or in the bra
in parenchyma may play a role in the pathophysiology of A beta -related vas
cular disorder.