title: Dopamine increases CD14+CD16+ monocyte migration and adhesion in the context of substance abuse and HIV neuropathogenesis.
abstract: Drug abuse is a major comorbidity of HIV infection and cognitive disorders are often more severe in the drug abusing HIV infected population. CD14+CD16+ monocytes, a mature subpopulation of peripheral blood monocytes, are key mediators of HIV neuropathogenesis. Infected CD14+CD16+ monocyte transmigration across the blood brain barrier mediates HIV entry into the brain and establishes a viral reservoir within the CNS. Despite successful antiretroviral therapy, continued influx of CD14+CD16+ monocytes, both infected and uninfected, contributes to chronic neuroinflammation and the development of HIV associated neurocognitive disorders (HAND). Drug abuse increases extracellular dopamine in the CNS. Once in the brain, CD14+CD16+ monocytes can be exposed to extracellular dopamine due to drug abuse. The direct effects of dopamine on CD14+CD16+ monocytes and their contribution to HIV neuropathogenesis are not known. In this study, we showed that CD14+CD16+ monocytes express mRNA for all five dopamine receptors by qRT-PCR and D1R, D5R and D4R surface protein by flow cytometry. Dopamine and the D1-like dopamine receptor agonist, SKF38393, increased CD14+CD16+ monocyte migration that was characterized as chemokinesis. To determine whether dopamine affected cell motility and adhesion, live cell imaging was used to monitor the accumulation of CD14+CD16+ monocytes on the surface of a tissue culture dish. Dopamine increased the number and the rate at which CD14+CD16+ monocytes in suspension settled to the dish surface. In a spreading assay, dopamine increased the area of CD14+CD16+ monocytes during the early stages of cell adhesion. In addition, adhesion assays showed that the overall total number of adherent CD14+CD16+ monocytes increased in the presence of dopamine. These data suggest that elevated extracellular dopamine in the CNS of HIV infected drug abusers contributes to HIV neuropathogenesis by increasing the accumulation of CD14+CD16+ monocytes in dopamine rich brain regions.
authors: Department of Pathology, Albert Einstein College of Medicine, Bronx, New York, United States of America.
authors: Jacqueline S
authors: JS
authors: Coley
authors: Department of Pathology, Albert Einstein College of Medicine, Bronx, New York, United States of America.
authors: Tina M
authors: TM
authors: Calderon
authors: Department of Pathology, Albert Einstein College of Medicine, Bronx, New York, United States of America.
authors: Peter J
authors: PJ
authors: Gaskill
authors: Public Health Research Institute, New Jersey Medical School, Rutgers University, Newark, New Jersey, United States of America.
authors: Eliseo A
authors: EA
authors: Eugenin
authors: Department of Pathology, Albert Einstein College of Medicine, Bronx, New York, United States of America; Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, United States of America.
authors: Joan W
authors: JW
authors: Berman
mesh_terms: D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D002448:Cell Adhesion; D002465:Cell Movement; D002478:Cells, Cultured; D004298:Dopamine / Q000378:metabolism*; D006678:HIV / Q000302:isolation & purification; D015658:HIV Infections / Q000150:complications* / Q000821:virology; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000032:analysis*; D009000:Monocytes / Q000166:cytology / Q000378:metabolism / Q000821:virology*; D017452:Receptors, IgG / Q000032:analysis*; D019966:Substance-Related Disorders / Q000150:complications* / Q000821:virology
chemical_list: D018950:Lipopolysaccharide Receptors; D017452:Receptors, IgG; D004298:Dopamine
references: Am J Pathol. 2009 Sep;175(3):1148-59
references: 19661443
references: Biosens Bioelectron. 2010 Jan 15;25(5):1179-85
references: 19896822
references: Neurobiol Dis. 2010 Mar;37(3):542-8
references: 20044002
references: J Leukoc Biol. 2010 Apr;87(4):621-6
references: 20130221
references: AIDS. 2010 Jun 1;24(9):1243-50
references: 19996937
references: Gut. 2010 Oct;59(10):1394-400
references: 20675697
references: J Acquir Immune Defic Syndr. 2010 Dec;55 Suppl 1:S10-6
references: 21045593
references: Neurology. 2010 Dec 7;75(23):2087-96
references: 21135382
references: J Neurovirol. 2011 Feb;17(1):3-16
references: 21174240
references: Cell Immunol. 2011;267(2):109-23
references: 21292246
references: Pharmacol Rev. 2011 Mar;63(1):182-217
references: 21303898
references: AIDS. 2011 Mar 13;25(5):625-33
references: 21297425
references: J Leukoc Biol. 2000 Apr;67(4):553-8
references: 10770289
references: J Neurovirol. 2000 May;6 Suppl 1:S82-5
references: 10871769
references: Virology. 2006 Jan 20;344(2):267-76
references: 16305804
references: J Neurosci. 2006 Jan 25;26(4):1098-106
references: 16436595
references: J Behav Med. 2011 Apr;34(2):128-38
references: 20857187
references: PLoS One. 2011;6(3):e17484
references: 21390263
references: J Neurochem. 2011 Apr;117(2):253-63
references: 21272002
references: Lancet. 2011 Aug 13;378(9791):571-83
references: 21802134
references: Aliment Pharmacol Ther. 2011 Oct;34(8):960-71
references: 21848603
references: J Viral Hepat. 2012 Feb;19(2):e89-96
references: 22239531
references: J Infect Dis. 2012 Jul 15;206(2):275-82
references: 22551810
references: J Acquir Immune Defic Syndr. 2012 Jul 1;60(3):234-43
references: 22569268
references: J Neuroinflammation. 2012;9:203
references: 22901451
references: J Neurovirol. 2013 Feb;19(1):65-74
references: 23250704
references: Bone. 2013 Sep;56(1):1-8
references: 23631878
references: PLoS One. 2013;8(7):e69270
references: 23922698
references: J Neuroimmune Pharmacol. 2014 Jun;9(3):302-12
references: 24682738
references: Acta Neuropathol. 2001 Feb;101(2):85-91
references: 11271377
references: J Exp Med. 2001 Apr 16;193(8):905-15
references: 11304551
references: J Neurovirol. 2001 Dec;7(6):528-41
references: 11704885
references: Hepatology. 2002 Feb;35(2):433-9
references: 11826420
references: J Acquir Immune Defic Syndr. 2002 Oct 1;31 Suppl 2:S35-42
references: 12394781
references: J Neuroimmunol. 2002 Nov;132(1-2):34-40
references: 12417431
references: J Int Neuropsychol Soc. 2003 Sep;9(6):847-54
references: 14632243
references: J Acquir Immune Defic Syndr. 2003 Dec 15;34(5):467-74
references: 14657756
references: Acta Neuropathol. 2004 Mar;107(3):216-26
references: 14712399
references: Trends Neurosci. 2004 May;27(5):270-7
references: 15111009
references: Am J Pathol. 2004 Jun;164(6):2089-99
references: 15161643
references: J Cell Sci. 2004 Sep 15;117(Pt 20):4619-28
references: 15371522
references: Virology. 1985 Nov;147(1):231-6
references: 2998068
references: Proc Natl Acad Sci U S A. 1988 Jul;85(14):5274-8
references: 2899326
references: Neuroscience. 1989;28(3):653-61
references: 2710338
references: J Neurochem. 1992 Jan;58(1):212-8
references: 1727431
references: J Neuropathol Exp Neurol. 1992 Mar;51(2):177-85
references: 1538241
references: Neurology. 1992 Sep;42(9):1736-9
references: 1513462
references: Eur J Immunol. 1993 Sep;23(9):2053-8
references: 7690321
references: J Neurosci. 1994 Oct;14(10):6084-93
references: 7931564
references: Clin Exp Immunol. 1994 Dec;98(3):369-74
references: 7527738
references: Proc Natl Acad Sci U S A. 1995 Dec 19;92(26):12304-8
references: 8618890
references: Eur J Immunol. 1995 Dec;25(12):3418-24
references: 8566032
references: J Exp Med. 1996 Sep 1;184(3):1101-9
references: 9064327
references: Lancet. 1997 Mar 8;349(9053):692-5
references: 9078201
references: Physiol Rev. 1998 Jan;78(1):189-225
references: 9457173
references: Proc Natl Acad Sci U S A. 1998 Feb 17;95(4):1840-5
references: 9465104
references: AIDS. 1998 Jul 30;12(11):1327-32
references: 9708412
references: J Immunol. 1998 Dec 15;161(12):6896-903
references: 9862722
references: J Hepatol. 2004 Nov;41(5):845-51
references: 15519659
references: J Recept Signal Transduct Res. 2004 Aug;24(3):165-205
references: 15521361
references: Neurology. 2005 Apr 26;64(8):1343-7
references: 15851720
references: Mol Cell Neurosci. 2005 May;29(1):128-38
references: 15866053
references: J Neuropathol Exp Neurol. 2005 Jun;64(6):529-36
references: 15977645
references: Nat Rev Neurosci. 2006 Jan;7(1):41-53
references: 16371949
references: J Immunol. 2006 Jan 15;176(2):848-56
references: 16393968
references: Curr HIV Res. 2014;12(2):85-96
references: 24862333
references: Mol Cell Biochem. 2000 Jan;203(1-2):113-7
references: 10724339
references: Am J Pathol. 2006 Mar;168(3):822-34
references: 16507898
references: Immunobiology. 2006;211(6-8):609-18
references: 16920499
references: Glia. 2006 Nov 1;54(6):619-29
references: 16944452
references: Curr Opin Pharmacol. 2007 Feb;7(1):69-76
references: 17174602
references: J Neuropsychiatry Clin Neurosci. 2007 Spring;19(2):157-63
references: 17431062
references: Trends Neurosci. 2007 May;30(5):188-93
references: 17368565
references: J Immunol. 2007 May 15;178(10):6581-9
references: 17475889
references: AIDS Res Hum Retroviruses. 2008 Mar;24(3):417-21
references: 18373432
references: J Neurovirol. 2008 Aug;14(4):318-26
references: 18780233
references: Lancet. 2008 Nov 15;372(9651):1733-45
references: 18817968
references: Eur J Neurosci. 2009 Jan;29(2):287-306
references: 19200235
references: Neuroscience. 2009 Jun 30;161(2):392-402
references: 19336247