Mononuclear phagocyte biophysiology influences brain transendothelial and tissue migration: implication for HIV-1-associated dementia.

Mononuclear phagocyte (MP) brain migration influence neuronal damage during HIV-1-associated dementia (HAD). We demonstrate that potassium channels, expressed in human monocyte-derived macrophages (MDM), are vital for MP movement through Boyden chemotactic chambers, an artificial blood-brain barrier and organotypic hippocampal brain slices. MDM migration is inhibited by voltage-and calcium-activated potassium channel blockers that include charybodotoxin, margatoxin, agatoxin and apamin. This is observed both in uninfected and HIV-1-infected MP. The results suggest that potassium channels affect MDM brain migration through altering cell volume and shape. Such mechanisms likely affect MP-induced neuronal destruction during HAD.