Functional characterization of the biogenic amine transporters on human macrophages
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 aroun...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Clinical investigation
2022-02-01
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| Series: | JCI Insight |
| Subjects: | |
| Online Access: | https://doi.org/10.1172/jci.insight.151892 |
| _version_ | 1811334858249601024 |
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| author | Phillip M. Mackie Adithya Gopinath Dominic M. Montas Alyssa Nielsen Aidan Smith Rachel A. Nolan Kaitlyn Runner Stephanie M. Matt John McNamee Joshua E. Riklan Kengo Adachi Andria Doty Adolfo Ramirez-Zamora Long Yan Peter J. Gaskill Wolfgang J. Streit Michael S. Okun Habibeh Khoshbouei |
| author_facet | Phillip M. Mackie Adithya Gopinath Dominic M. Montas Alyssa Nielsen Aidan Smith Rachel A. Nolan Kaitlyn Runner Stephanie M. Matt John McNamee Joshua E. Riklan Kengo Adachi Andria Doty Adolfo Ramirez-Zamora Long Yan Peter J. Gaskill Wolfgang J. Streit Michael S. Okun Habibeh Khoshbouei |
| author_sort | Phillip M. Mackie |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T17:15:34Z |
| format | Article |
| id | doaj.art-263453e666ba4697b86326efb160a36d |
| institution | Directory Open Access Journal |
| issn | 2379-3708 |
| language | English |
| last_indexed | 2024-04-13T17:15:34Z |
| publishDate | 2022-02-01 |
| publisher | American Society for Clinical investigation |
| record_format | Article |
| series | JCI Insight |
| spelling | doaj.art-263453e666ba4697b86326efb160a36d2022-12-22T02:38:09ZengAmerican Society for Clinical investigationJCI Insight2379-37082022-02-0174Functional characterization of the biogenic amine transporters on human macrophagesPhillip M. MackieAdithya GopinathDominic M. MontasAlyssa NielsenAidan SmithRachel A. NolanKaitlyn RunnerStephanie M. MattJohn McNameeJoshua E. RiklanKengo AdachiAndria DotyAdolfo Ramirez-ZamoraLong YanPeter J. GaskillWolfgang J. StreitMichael S. OkunHabibeh KhoshboueiMonocyte-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.https://doi.org/10.1172/jci.insight.151892InflammationNeuroscience |
| spellingShingle | Phillip M. Mackie Adithya Gopinath Dominic M. Montas Alyssa Nielsen Aidan Smith Rachel A. Nolan Kaitlyn Runner Stephanie M. Matt John McNamee Joshua E. Riklan Kengo Adachi Andria Doty Adolfo Ramirez-Zamora Long Yan Peter J. Gaskill Wolfgang J. Streit Michael S. Okun Habibeh Khoshbouei Functional characterization of the biogenic amine transporters on human macrophages JCI Insight Inflammation Neuroscience |
| title | Functional characterization of the biogenic amine transporters on human macrophages |
| title_full | Functional characterization of the biogenic amine transporters on human macrophages |
| title_fullStr | Functional characterization of the biogenic amine transporters on human macrophages |
| title_full_unstemmed | Functional characterization of the biogenic amine transporters on human macrophages |
| title_short | Functional characterization of the biogenic amine transporters on human macrophages |
| title_sort | functional characterization of the biogenic amine transporters on human macrophages |
| topic | Inflammation Neuroscience |
| url | https://doi.org/10.1172/jci.insight.151892 |
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