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Journal article
Functional characterization of the biogenic amine transporters on human macrophages
JCI insight, v 7(4)
22 Feb 2022
PMID: 35015729
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Monocyte-derived macrophages (MDMs) are key players in tissue homeostasis and diseases regulated by a variety of signaling molecules. Recent literature has highlighted the ability for biogenic amines to regulate macrophage functions, but the mechanisms governing biogenic amine signaling in and around immune cells remain nebulous. In the CNS, biogenic amine transporters are regarded as the master regulators of neurotransmitter signaling. While we and others have shown that macrophages express these transporters, relatively little is known of their function in these cells. To address these knowledge gaps, we investigated the function of norepinephrine transporter (NET) and dopamine transporter (DAT) on human MDMs. We found that both NET and DAT are present and can uptake substrate from the extracellular space at baseline. Not only was DAT expressed in cultured MDMs, but it was also detected in a subset of intestinal macrophages in situ. Surprisingly, we discovered a NET-independent, DAT-mediated immunomodulatory mechanism in response to LPS. LPS induced reverse transport of dopamine through DAT, engaging an autocrine/paracrine signaling loop that regulated the macrophage response. Removing this signaling loop enhanced the proinflammatory response to LPS. Our data introduce a potential role for DAT in the regulation of innate immunity.
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Details
- Title
- Functional characterization of the biogenic amine transporters on human macrophages
- Creators
- Phillip M Mackie - Department of Neuroscience, University of Florida College of Medicine, Gainesville, Florida, USAAdithya Gopinath - Department of Neuroscience, University of Florida College of Medicine, Gainesville, Florida, USADominic M Montas - Department of Neuroscience, University of Florida College of Medicine, Gainesville, Florida, USAAlyssa Nielsen - Department of Neuroscience, University of Florida College of Medicine, Gainesville, Florida, USAAidan Smith - Department of Neuroscience, University of Florida College of Medicine, Gainesville, Florida, USARachel A Nolan - Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, Pennsylvania, USAKaitlyn Runner - Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, Pennsylvania, USAStephanie M Matt - Drexel UniversityJohn McNamee - Department of Neuroscience, University of Florida College of Medicine, Gainesville, Florida, USAJoshua E Riklan - Department of Neuroscience, University of Florida College of Medicine, Gainesville, Florida, USAKengo Adachi - Neuronal Signal Transduction Group, Max Planck Florida Institute for Neuroscience, Jupiter, Florida, USAAndria Doty - Interdiscipinary Center for Biotechnology Research, University of Florida, Gainesville, Florida, USAAdolfo Ramirez-Zamora - Department of NeurologyLong Yan - Neuronal Signal Transduction Group, Max Planck Florida Institute for Neuroscience, Jupiter, Florida, USAPeter J Gaskill - Drexel UniversityWolfgang J Streit - Department of Neuroscience, University of Florida College of Medicine, Gainesville, Florida, USAMichael S Okun - Center for Translational Research in Neurodegenerative Disease, University of Florida College of Medicine, Gainesville, Florida, USAHabibeh Khoshbouei - Department of Neuroscience, University of Florida College of Medicine, Gainesville, Florida, USA
- Publication Details
- JCI insight, v 7(4)
- Publisher
- American Society for Clinical Investigation
- Grant note
- R21 DA043895 / NIDA NIH HHS TL1 TR001428 / NCATS NIH HHS R01 DA026947 / NIDA NIH HHS R01 DK071122 / NIDDK NIH HHS UL1 TR001427 / NCATS NIH HHS S10 OD020026 / NIH HHS R01 NS071122 / NINDS NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000760416700001
- Scopus ID
- 2-s2.0-85125020596
- Other Identifier
- 991019167692504721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Medicine, Research & Experimental