title: Dopamine Increases CD14+CD16+Monocyte Transmigration across the Blood Brain Barrier: Implications for Substance Abuse and HIV Neuropathogenesis.
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.
authors.affiliation: Department of Pathology, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
authors.forename: Tina M
authors.initials: TM
authors.lastname: Calderon
authors.affiliation: Department of Pathology, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
authors.forename: Dionna W
authors.initials: DW
authors.lastname: Williams
authors.affiliation: Department of Pathology, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
authors.forename: Lillie
authors.initials: L
authors.lastname: Lopez
authors.affiliation: Public Health Research Institute (PHRI), New Jersey Medical School, Rutgers The State University of New Jersey, Newark, NJ, 07103, USA.|Department of Microbiology and Molecular Genetics, New Jersey Medical School, Rutgers The State University of New Jersey, Newark, NJ, 07103, USA.
authors.forename: Eliseo A
authors.initials: EA
authors.lastname: Eugenin
authors.affiliation: Department of Pathology, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.|Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Cheney
authors.affiliation: Department of Pathology, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Gaskill
authors.affiliation: Department of Pathology, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
authors.forename: Mike
authors.initials: M
authors.lastname: Veenstra
authors.affiliation: Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.|Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.|Department of Obstetrics and Gynecology and Women's Health, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Anastos
authors.affiliation: Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.|Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.|Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Morgello
authors.affiliation: Department of Pathology, Albert Einstein College of Medicine, Bronx, NY, 10461, USA. joan.berman@einstein.yu.edu.|Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, 10461, USA. joan.berman@einstein.yu.edu.
authors.forename: Joan W
authors.initials: JW
authors.lastname: Berman
mesh_terms: D000328:Adult; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D015331:Cohort Studies; D004298:Dopamine / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D015658:HIV Infections / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D017452:Receptors, IgG / Q000378:metabolism*; D019966:Substance-Related Disorders / Q000378:metabolism* / Q000473:pathology; D057705:Transendothelial and Transepithelial Migration / Q000187:drug effects / Q000502:physiology
chemical_list: D018950:Lipopolysaccharide Receptors; D017452:Receptors, IgG; D004298:Dopamine
keywords: CD14+CD16+ monocytes; CNS HIV reservoirs; Dopamine; HAND; Neuroinflammation; Substance abuse