دورية أكاديمية
Targeting foamy macrophages by manipulating ABCA1 expression to facilitate lesion healing in the injured spinal cord.
العنوان: | Targeting foamy macrophages by manipulating ABCA1 expression to facilitate lesion healing in the injured spinal cord. |
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المؤلفون: | Wang X; W. M. Keck Center for Collaborative Neuroscience, Rutgers, State University of New Jersey, New Brunswick, NJ 08854, USA; Institute of Neurosciences, Fourth Military Medical University, Xi'an 710032, China; College of Life Sciences and Medicine, Northwest University, Xi'an 710069, China. Electronic address: wangzh@fmmu.edu.cn., Cheng Z; Department of Biomedical Sciences, Florida State University College of Medicine, 1115 West Call Street, Tallahassee, FL 32306, USA., Tai W; Department of Biomedical Sciences, Florida State University College of Medicine, 1115 West Call Street, Tallahassee, FL 32306, USA., Shi M; Department of Biomedical Sciences, Florida State University College of Medicine, 1115 West Call Street, Tallahassee, FL 32306, USA., Ayazi M; Department of Biomedical Sciences, Florida State University College of Medicine, 1115 West Call Street, Tallahassee, FL 32306, USA., Liu Y; Department of Biomedical Sciences, Florida State University College of Medicine, 1115 West Call Street, Tallahassee, FL 32306, USA., Sun L; Department of Biomedical Sciences, Florida State University College of Medicine, 1115 West Call Street, Tallahassee, FL 32306, USA., Yu C; Institute of Neurosciences, Fourth Military Medical University, Xi'an 710032, China., Fan Z; Department of Critical Care Medicine and Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, Xi'an 710032, China., Guo B; Department of Pathology, Guizhou Medical University, Guiyang 550025, China., He X; Department of Orthopedics, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China., Sun D; W. M. Keck Center for Collaborative Neuroscience, Rutgers, State University of New Jersey, New Brunswick, NJ 08854, USA., Young W; W. M. Keck Center for Collaborative Neuroscience, Rutgers, State University of New Jersey, New Brunswick, NJ 08854, USA., Ren Y; W. M. Keck Center for Collaborative Neuroscience, Rutgers, State University of New Jersey, New Brunswick, NJ 08854, USA; Department of Biomedical Sciences, Florida State University College of Medicine, 1115 West Call Street, Tallahassee, FL 32306, USA. Electronic address: yi.ren@med.fsu.edu. |
المصدر: | Brain, behavior, and immunity [Brain Behav Immun] 2024 Jul; Vol. 119, pp. 431-453. Date of Electronic Publication: 2024 Apr 16. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: Elsevier Country of Publication: Netherlands NLM ID: 8800478 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1090-2139 (Electronic) Linking ISSN: 08891591 NLM ISO Abbreviation: Brain Behav Immun Subsets: MEDLINE |
أسماء مطبوعة: | Publication: <2000- > : Amsterdam : Elsevier Original Publication: San Diego : Academic Press, [c1987- |
مواضيع طبية MeSH: | ATP Binding Cassette Transporter 1*/metabolism , Spinal Cord Injuries*/metabolism , Macrophages*/metabolism, Animals ; Mice ; Male ; Foam Cells/metabolism ; Mice, Inbred C57BL ; Spinal Cord/metabolism ; Mice, Knockout ; Disease Models, Animal |
مستخلص: | Spinal cord injury (SCI) triggers a complex cascade of events, including myelin loss, neuronal damage, neuroinflammation, and the accumulation of damaged cells and debris at the injury site. Infiltrating bone marrow derived macrophages (BMDMϕ) migrate to the epicenter of the SCI lesion, where they engulf cell debris including abundant myelin debris to become pro-inflammatory foamy macrophages (foamy Mϕ), participate neuroinflammation, and facilitate the progression of SCI. This study aimed to elucidate the cellular and molecular mechanisms underlying the functional changes in foamy Mϕ and their potential implications for SCI. Contusion at T10 level of the spinal cord was induced using a New York University (NYU) impactor (5 g rod from a height of 6.25 mm) in male mice. ABCA1, an ATP-binding cassette transporter expressed by Mϕ, plays a crucial role in lipid efflux from foamy cells. We observed that foamy Mϕ lacking ABCA1 exhibited increased lipid accumulation and a higher presence of lipid-accumulated foamy Mϕ as well as elevated pro-inflammatory response in vitro and in injured spinal cord. We also found that both genetic and pharmacological enhancement of ABCA1 expression accelerated lipid efflux from foamy Mϕ, reduced lipid accumulation and inhibited the pro-inflammatory response of foamy Mϕ, and accelerated clearance of cell debris and necrotic cells, which resulted in functional recovery. Our study highlights the importance of understanding the pathologic role of foamy Mϕ in SCI progression and the potential of ABCA1 as a therapeutic target for modulating the inflammatory response, promoting lipid metabolism, and facilitating functional recovery in SCI. (Copyright © 2024. Published by Elsevier Inc.) |
فهرسة مساهمة: | Keywords: ABCA1; Bone marrow derived macrophages; Foamy macrophages; Lipid accumulation; Lipid efflux; Pro-inflammation; Spinal cord debris; Spinal cord injury |
المشرفين على المادة: | 0 (ATP Binding Cassette Transporter 1) 0 (Abca1 protein, mouse) |
تواريخ الأحداث: | Date Created: 20240418 Date Completed: 20240609 Latest Revision: 20240618 |
رمز التحديث: | 20240618 |
DOI: | 10.1016/j.bbi.2024.04.013 |
PMID: | 38636566 |
قاعدة البيانات: | MEDLINE |
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