دورية أكاديمية
Morphine disrupts macrophage functions even during HIV infection.
| العنوان: | Morphine disrupts macrophage functions even during HIV infection. |
|---|---|
| المؤلفون: | Barbaro JM; Department of Pathology, Albert Einstein College of Medicine, Bronx, New York, USA., Jaureguiberry-Bravo M; Department of Pathology, Albert Einstein College of Medicine, Bronx, New York, USA., Sidoli S; Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York, USA., Berman JW; Department of Pathology, Albert Einstein College of Medicine, Bronx, New York, USA.; Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, USA. |
| المصدر: | Journal of leukocyte biology [J Leukoc Biol] 2022 Nov; Vol. 112 (5), pp. 1317-1328. Date of Electronic Publication: 2022 Oct 07. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Oxford University Press Country of Publication: England NLM ID: 8405628 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1938-3673 (Electronic) Linking ISSN: 07415400 NLM ISO Abbreviation: J Leukoc Biol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2023- : Oxford : Oxford University Press Original Publication: New York : Alan R. Liss, c1984- |
| مواضيع طبية MeSH: | HIV Infections*/metabolism, Humans ; Morphine/pharmacology ; Morphine/metabolism ; Analgesics, Opioid/pharmacology ; Analgesics, Opioid/metabolism ; Heroin/metabolism ; Heroin/pharmacology ; Quality of Life ; Reactive Oxygen Species/metabolism ; Proteomics ; Macrophages/metabolism ; Receptors, Opioid/metabolism |
| مستخلص: | HIV-associated neurocognitive impairment (HIV-NCI) is a debilitating comorbidity that reduces quality of life in 15-40% of people with HIV (PWH) taking antiretroviral therapy (ART). Opioid use has been shown to increase neurocognitive deficits in PWH. Monocyte-derived macrophages (MDMs) harbor HIV in the CNS even in PWH on ART. We hypothesized that morphine (MOR), a metabolite of heroin, further dysregulates functional processes in MDMs to increase neuropathogenesis. We found that, in uninfected and HIV-infected primary human MDMs, MOR activates these cells by increasing phagocytosis and up-regulating reactive oxygen species. Effects of MOR on phagocytosis were dependent on μ-opioid receptor activity and were mediated, in part, by inhibited lysosomal degradation of phagocytized substrates. All results persisted when cells were treated with both MOR and a commonly prescribed ART cocktail, suggesting minimal impact of ART during opioid exposure. We then performed mass spectrometry in HIV-infected MDMs treated with or without MOR to determine proteomic changes that suggest additional mechanisms by which opioids affect macrophage homeostasis. Using downstream pathway analyses, we found that MOR dysregulates ER quality control and extracellular matrix invasion. Our data indicate that MOR enhances inflammatory functions and impacts additional cellular processes in HIV-infected MDMs to potentially increases neuropathogenesis in PWH using opioids. (©2022 Society for Leukocyte Biology.) |
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| معلومات مُعتمدة: | S10 OD030286 United States OD NIH HHS; R01 DA044584 United States DA NIDA NIH HHS; P30 AI124414 United States AI NIAID NIH HHS; F30 DA053118 United States DA NIDA NIH HHS; T32 GM007288 United States GM NIGMS NIH HHS; P30 CA013330 United States CA NCI NIH HHS; R01 DA048609 United States DA NIDA NIH HHS |
| فهرسة مساهمة: | Keywords: ER quality control; HIV-NCI; ROS; VEGFR2 signaling; antiretroviral therapy; myeloid cells; opioid receptors; opioids; phagocytosis; proteomics |
| المشرفين على المادة: | 76I7G6D29C (Morphine) 0 (Analgesics, Opioid) 70D95007SX (Heroin) 0 (Reactive Oxygen Species) 0 (Receptors, Opioid) |
| تواريخ الأحداث: | Date Created: 20221007 Date Completed: 20221027 Latest Revision: 20231102 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC9677813 |
| DOI: | 10.1002/JLB.3MA0522-273RR |
| PMID: | 36205434 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1938-3673 |
|---|---|
| DOI: | 10.1002/JLB.3MA0522-273RR |