Dopamine Increases CD14+CD16+ Monocyte Transmigration across the Blood Brain Barrier

Implications for Substance Abuse and HIV Neuropathogenesis

Tina M. Calderon, Dionna W. Williams, Lillie Lopez, Eliseo Eugenin, Laura Cheney, Peter J. Gaskill, Mike Veenstra, Kathryn Anastos, Susan Morgello, Joan W. Berman

Research output: Contribution to journalArticle

8 Citations (Scopus)

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 CD14+CD16+ monocytes mediate HIV entry into the central nervous system (CNS) and that uninfected and infected CD14+CD16+ 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 CD14+CD16+ 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 CD14+CD16+ 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 CD14+CD16+ 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 CD14+CD16+ 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.

Original languageEnglish (US)
Pages (from-to)353-370
Number of pages18
JournalJournal of NeuroImmune Pharmacology
Volume12
Issue number2
DOIs
StatePublished - Jun 1 2017
Externally publishedYes

Fingerprint

Blood-Brain Barrier
Substance-Related Disorders
HIV-1
Monocytes
Dopamine
Central Nervous System
2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
Dopamine D1 Receptors
Virus Internalization
Dopamine Agonists
Neurotransmitter Agents
Flow Cytometry
HIV
Pharmaceutical Preparations

Keywords

  • CD14CD16 monocytes
  • CNS HIV reservoirs
  • Dopamine
  • HAND
  • Neuroinflammation
  • Substance abuse

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Immunology and Allergy
  • Immunology
  • Pharmacology

Cite this

Dopamine Increases CD14+CD16+ Monocyte Transmigration across the Blood Brain Barrier : Implications for Substance Abuse and HIV Neuropathogenesis. / Calderon, Tina M.; Williams, Dionna W.; Lopez, Lillie; Eugenin, Eliseo; Cheney, Laura; Gaskill, Peter J.; Veenstra, Mike; Anastos, Kathryn; Morgello, Susan; Berman, Joan W.

In: Journal of NeuroImmune Pharmacology, Vol. 12, No. 2, 01.06.2017, p. 353-370.

Research output: Contribution to journalArticle

Calderon, Tina M. ; Williams, Dionna W. ; Lopez, Lillie ; Eugenin, Eliseo ; Cheney, Laura ; Gaskill, Peter J. ; Veenstra, Mike ; Anastos, Kathryn ; Morgello, Susan ; Berman, Joan W. / Dopamine Increases CD14+CD16+ Monocyte Transmigration across the Blood Brain Barrier : Implications for Substance Abuse and HIV Neuropathogenesis. In: Journal of NeuroImmune Pharmacology. 2017 ; Vol. 12, No. 2. pp. 353-370.
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