Targeting foamy macrophages by manipulating ABCA1 expression to facilitate lesion healing in the injured spinal cord.
Brain Behav Immun
; 119: 431-453, 2024 Jul.
Article
in En
| MEDLINE
| ID: mdl-38636566
ABSTRACT
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 (BMDMÏ) migrate to the epicenter of the SCI lesion, where they engulf cell debris including abundant myelin debris to become pro-inflammatory foamy macrophages (foamy MÏ), participate neuroinflammation, and facilitate the progression of SCI. This study aimed to elucidate the cellular and molecular mechanisms underlying the functional changes in foamy MÏ 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 MÏ, plays a crucial role in lipid efflux from foamy cells. We observed that foamy MÏ lacking ABCA1 exhibited increased lipid accumulation and a higher presence of lipid-accumulated foamy MÏ 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 MÏ, reduced lipid accumulation and inhibited the pro-inflammatory response of foamy MÏ, 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 MÏ 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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Spinal Cord Injuries
/
ATP Binding Cassette Transporter 1
/
Macrophages
Limits:
Animals
Language:
En
Journal:
Brain Behav Immun
Journal subject:
ALERGIA E IMUNOLOGIA
/
CEREBRO
/
PSICOFISIOLOGIA
Year:
2024
Document type:
Article