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.
Chung
Induk
I
The Center for Neurovirology and Neurodegenerative Disorders, Departments of Pathology and Microbiology, University of Nebraska Medical Center, 985215 Nebraska Medical Center, Omaha, NE 68198-5215, USA.
Zelivyanskaya
Marina
M
Gendelman
Howard E
HE
D015526:AIDS Dementia Complex / Q000276:immunology*; D001812:Blood-Brain Barrier / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D018999:Charybdotoxin / Q000494:pharmacology; D015194:Diffusion Chambers, Culture; D015497:HIV-1; D006624:Hippocampus / Q000166:cytology / Q000276:immunology; D006801:Humans; D018613:Microscopy, Confocal; D009000:Monocytes / Q000166:cytology* / Q000502:physiology*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D010587:Phagocytosis / Q000502:physiology*; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000502:physiology
D015221:Potassium Channels; D018999:Charybdotoxin; D011188:Potassium