Dopamine Increases CD14CD16 Monocyte Transmigration across the Blood Brain Barrier: Implications for Substance Abuse and HIV Neuropathogenesis.

TitleDopamine Increases CD14CD16 Monocyte Transmigration across the Blood Brain Barrier: Implications for Substance Abuse and HIV Neuropathogenesis.
Publication TypeJournal Article
Year of Publication2017
AuthorsCalderon, TM, Williams, DW, Lopez, L, Eugenin, EA, Cheney, L, Gaskill, PJ, Veenstra, M, Anastos, K, Morgello, S, Berman, JW
JournalJ Neuroimmune Pharmacol
Volume12
Issue2
Pagination353-370
Date Published2017 Jun
ISSN1557-1904
KeywordsAdult, Blood-Brain Barrier, Cells, Cultured, Cohort Studies, dopamine, Female, HIV Infections, Humans, Lipopolysaccharide Receptors, Male, Middle Aged, Monocytes, Receptors, IgG, Substance-Related Disorders, Transendothelial and Transepithelial Migration
Abstract

In human immunodeficiency virus-1 (HIV) infected individuals, substance abuse may accelerate the development and/or increase the severity of HIV associated neurocognitive disorders (HAND). It is proposed that CD14CD16 monocytes mediate HIV entry into the central nervous system (CNS) and that uninfected and infected CD14CD16 monocyte transmigration across the blood brain barrier (BBB) contributes to the establishment and propagation of CNS HIV viral reservoirs and chronic neuroinflammation, important factors in the development of HAND. The effects of substance abuse on the frequency of CD14CD16 monocytes in the peripheral circulation and on the entry of these cells into the CNS during HIV neuropathogenesis are not known. PBMC from HIV infected individuals were analyzed by flow cytometry and we demonstrate that the frequency of peripheral blood CD14CD16 monocytes in HIV infected substance abusers is increased when compared to those without active substance use. Since drug use elevates extracellular dopamine concentrations in the CNS, we examined the effects of dopamine on CD14CD16 monocyte transmigration across our in vitro model of the human BBB. The transmigration of this monocyte subpopulation is increased by dopamine and the dopamine receptor agonist, SKF 38393, implicating D1-like dopamine receptors in the increase in transmigration elicited by this neurotransmitter. Thus, elevated extracellular CNS dopamine may be a novel common mechanism by which active substance use increases uninfected and HIV infected CD14CD16 monocyte transmigration across the BBB. The influx of these cells into the CNS may increase viral seeding and neuroinflammation, contributing to the development of HIV associated neurocognitive impairments.

DOI10.1007/s11481-017-9726-9
Alternate JournalJ Neuroimmune Pharmacol
PubMed ID28133717
PubMed Central IDPMC5406247
Grant ListR01 DA025567 / DA / NIDA NIH HHS / United States
U24 MH100931 / MH / NIMH NIH HHS / United States
U01 AI035004 / AI / NIAID NIH HHS / United States
P30 AI051519 / AI / NIAID NIH HHS / United States
R01 MH096625 / MH / NIMH NIH HHS / United States
R25 MH080663 / MH / NIMH NIH HHS / United States
R01 DA039005 / DA / NIDA NIH HHS / United States
K01 DA029476 / DA / NIDA NIH HHS / United States
U01 MH083501 / MH / NIMH NIH HHS / United States
P30 AI124414 / AI / NIAID NIH HHS / United States
R01 MH090958 / MH / NIMH NIH HHS / United States
K99 DA044838 / DA / NIDA NIH HHS / United States
R01 MH075679 / MH / NIMH NIH HHS / United States