Journal article
Characterization and function of the human macrophage dopaminergic system: implications for CNS disease and drug abuse
Journal of neuroinflammation, v 9(1), pp 203-203
18 Aug 2012
PMID: 22901451
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Background: Perivascular macrophages and microglia are critical to CNS function. Drugs of abuse increase extracellular dopamine in the CNS, exposing these cells to elevated levels of dopamine. In rodent macrophages and human T-cells, dopamine was shown to modulate cellular functions through activation of dopamine receptors and other dopaminergic proteins. The expression of these proteins and the effects of dopamine on human macrophage functions had not been studied.
Methods: To study dopaminergic gene expression, qRT-PCR was performed on mRNA from primary human monocyte derived macrophages (MDM). Expression and localization of dopaminergic proteins was examined by immunoblotting isolated plasma membrane, total membrane and cytosolic proteins from MDM. To characterize dopamine-mediated changes in cytokine production in basal and inflammatory conditions, macrophages were treated with different concentrations of dopamine in the presence or absence of LPS and cytokine production was assayed by ELISA. Statistical significance was determined using two-tailed Students' T-tests or Wilcoxen Signed Rank tests.
Results: These data show that MDM express mRNA for all five subtypes of dopamine receptors, and that dopamine receptors 3 and 4 are expressed on the plasma membrane. MDM also express mRNA for the dopamine transporter (DAT), vesicular monoamine transporter 2 (VMAT2), tyrosine hydroxylase (TH) and aromatic amino acid decarboxylase (AADC). DAT is expressed on the plasma membrane, VMAT2 on cellular membranes and TH and AADC are in the cytosol. Dopamine also alters macrophage cytokine production in both untreated and LPS-treated cells. Untreated macrophages show dopamine mediated increases IL-6 and CCL2. Macrophages treated with LPS show increased IL-6, CCL2, CXCL8 and IL-10 and decreased TNF-alpha.
Conclusions: Monocyte derived macrophages express dopamine receptors and other dopaminergic proteins through which dopamine may modulate macrophage functions. Thus, increased CNS dopamine levels due to drug abuse may exacerbate the development of neurological diseases including Alzheimer's disease and HIV associated neurological disorders.
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Details
- Title
- Characterization and function of the human macrophage dopaminergic system: implications for CNS disease and drug abuse
- Creators
- Peter J. Gaskill - Albert Einstein College of MedicineLoreto Carvallo - Albert Einstein College of MedicineEliseo A. Eugenin - Albert Einstein College of MedicineJoan W. Berman - Albert Einstein College of Medicine
- Publication Details
- Journal of neuroinflammation, v 9(1), pp 203-203
- Publisher
- Springer Nature
- Number of pages
- 14
- Grant note
- MH096625; MH090958; MH075679 / National Institutes of Mental Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Mental Health (NIMH) R01DA025567 / NATIONAL INSTITUTE ON DRUG ABUSE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Drug Abuse (NIDA); European Commission R01MH075679 / NATIONAL INSTITUTE OF MENTAL HEALTH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Mental Health (NIMH) DA029476; DA026149; DA25567 / National Institutes of Drug Abuse; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Drug Abuse (NIDA)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- College of Medicine; Pharmacology and Physiology; Drexel University
- Web of Science ID
- WOS:000310803400001
- Scopus ID
- 2-s2.0-84865053439
- Other Identifier
- 991020099769304721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Immunology
- Neurosciences