Macrophage Extracellular Traps Exacerbate Secondary Spinal Cord Injury by Modulating Macrophage/Microglia Polarization via LL37/P2X7R/NF-κB Signaling Pathway

Oxidative Medicine and Cellular Longevity, 2022 · DOI: https://doi.org/10.1155/2022/9197940 · Published: November 23, 2022

Spinal Cord Injury Genetics

Simple Explanation

Spinal cord injury can cause persistent inflammation, hindering nerve repair due to overactive immune cells called macrophages and microglia. Macrophages can release extracellular traps (Met), a form of cell death, which may contribute to this inflammation. This study found that Mets are present in spinal cord injuries and promote inflammation by causing macrophages/microglia to become a type that worsens the injury (M1-like). Limiting Mets can reduce this inflammation and aid recovery. The study also found that Met-related proteins in human serum correlate with the severity of spinal cord injury, suggesting Mets could be a target for therapy and an assessment marker.

Study Duration

28 days

Participants

96 Sprague-Dawley rats and 32 human subjects

Evidence Level

Not specified

Key Findings

1
Macrophages in the injured spinal cord release Mets, which contribute to the differentiation of macrophage/microglia into M1-like cells, exacerbating inflammation.
2
Limiting the number of Mets through DNase I injection promoted functional recovery and nerve conduction after spinal cord injury in rats.
3
The concentration levels of cf-DNA, CD68, and CitH3 in human serum correlate with the stage and severity of spinal cord injury, as indicated by ASIA scores.

Research Summary

This study investigates the role of macrophage extracellular traps (Mets) in secondary spinal cord injury (SCI). The research demonstrates that Mets exacerbate inflammation by promoting M1 polarization of macrophage/microglia. The study identifies a novel extracellular pro-inflammatory signaling pathway involving LL37/P2X7R/NF-κB, through which Mets modulate macrophage/microglia polarization. The research suggests that targeting Mets may offer a new therapeutic approach for SCI, and Met-related markers in human serum could serve as potential indices for SCI assessment.

Practical Implications

Therapeutic Target

Mets may represent a novel therapeutic target for reducing inflammation and promoting recovery in spinal cord injury.

Diagnostic Marker

Met-related proteins in human serum may serve as potential biomarkers for assessing the severity and stage of SCI in clinical settings.

Signaling Pathway

Targeting the LL37/P2X7R/NF-κB signaling pathway could offer a strategy to modulate macrophage/microglia polarization and reduce inflammation in SCI.

Study Limitations

1
Further in-vitro experiments are needed to verify this extracellular regulatory mechanism.
2
Whether Mets can promote inflammation through other potential mechanisms remains to be studied.
3
Further in-vitro experiments need to be carried out to explore the diﬀerence in M1 polarization of macrophage and microglia induced by Mets, respectively.

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