Induction of CD40 on human endothelial cells by Alzheimer's beta-amyloid peptides

Growing evidence suggests that beta-amyloid (A beta) peptides play a centra l role in mediating vascular endothelium dysfunction, but the extent to whi ch immune mechanisms are involved in this process remains unclear. To explo re such mechanisms, we incubated cultured human aortic endothelial cells (H AEC) with freshly solublized A beta and examined expression of a central im munoregulatory molecule, CD40, in these cells using reverse transcriptase-p olymerase chain reaction, Western immunoblotting, and Flow cytometry, Our r esults show that treatment of endothelial cells with A beta(1-40), A beta(1 -42) or gamma interferon (IFN-gamma) results in a dose-dependent induction of endothelial CD40 expression. Furthermore, ligation of endothelial CD40 a nd simultaneous treatment of human endothelial cells with lFN-gamma or A be ta peptides leads to a significant release of interleukin-1;beta (IL-1 beta ), a marker for endothelial cell activation. Since IL-1 beta is an importan t inflammatory response mediator, these findings suggest that the functiona l role of A beta-induced endothelial CD40 may be promotion of the inflammat ory cascade in vascular endothelial cells. (C) 1999 Elsevier Science Inc.