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  Functional characterization of the biogenic amine transporters on human macrophages

Mackie, P. M., Gopinath, A., Montas, D. M., Nielsen, A., Smith, A., Nolan, R. A., et al. (2022). Functional characterization of the biogenic amine transporters on human macrophages. JCI insight, (4). Retrieved from https://insight.jci.org/articles/view/151892/files/pdf.

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Item Permalink: https://hdl.handle.net/21.11116/0000-000B-FBE7-6 Version Permalink: https://hdl.handle.net/21.11116/0000-000B-FBE8-5
Genre: Journal Article
Alternative Title : JCI insight

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 Creators:
Mackie, Phillip M., Author
Gopinath, Adithya, Author
Montas, Dominic M., Author
Nielsen, Alyssa, Author
Smith, Aidan, Author
Nolan, Rachel A., Author
Runner, Kaitlyn, Author
Matt, Stephanie M., Author
McNamee, John, Author
Riklan, Joshua E., Author
Adachi, Kengo1, Author
Doty, Andria, Author
Ramirez-Zamora, Adolfo, Author
Yan, Long1, Author
Gaskill, Peter J., Author
Streit, Wolfgang J., Author
Okun, Michael S., Author
Khoshbouei, Habibeh, Author
Affiliations:
1Max Planck Florida Institute for Neuroscience, Max Planck Society, One Max Planck Way, Jupiter FL 33458, USA, ou_1950288              

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Free keywords: Male, Adult, Female, Humans, Neuroscience, Gene Expression Regulation, RNA, Aged, Middle Aged, Young Adult, Biogenic Amines, Biological Transport, Dopamine Plasma Membrane Transport Proteins, Inflammation, Innate immunity, Macrophages, Transport
 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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 Dates: 2022
 Publication Status: Issued
 Pages: -
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 Rev. Type: -
 Identifiers: URI: https://insight.jci.org/articles/view/151892/files/pdf
URI: http://www.ncbi.nlm.nih.gov/pubmed/35015729
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Title: JCI insight
  Alternative Title : JCI Insight
Source Genre: Journal
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Publ. Info: -
Pages: e151892 Volume / Issue: (4) Sequence Number: - Start / End Page: - Identifier: ISBN: 2379-3708