CD47-blocking antibody interferes with neutrophil extracellular traps formation after spinal cord injury to reduce spinal cord edema.

1. J Neuroimmunol. 2025 Mar 15;400:578553. doi: 10.1016/j.jneuroim.2025.578553. Epub 2025 Feb 10.

CD47-blocking antibody interferes with neutrophil extracellular traps formation after spinal cord injury to reduce spinal cord edema.

Diao Y(1), Hao M(1), Xie M(1), Hu X(1), Tan R(1), Wang Z(1), Rong H(1), Zhu T(2).

Author information: (1)Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300000, China. (2)Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300000, China. Electronic address: zhutao5@tmu.edu.cn.

OBJECTIVE: Our goal was to investigate the role of neutrophil extracellular traps (NETs) in the disruption of the blood-spinal cord barrier (BSCB) following spinal cord injury (SCI) and to evaluate the therapeutic efficacy of CD47-blocking antibodies in mitigating the disruption. METHODS: We utilized Evans blue extravasation to evaluate BSCB permeability and immunofluorescence to evaluate the formation of NETs and the expression of ZO-1, CD31, S100A8/A9, CD68, GFAP, Iba-1, and NeuN. Spinal cord edema was quantified by comparing the dry and wet weights of tissue samples. We used enzyme-linked immunosorbent assay (ELISA) to evaluate inflammatory factors, including IL-1β, IL-6, and TNF-α. Changes in genes associated with NET formation were identified by mRNA sequencing. Activation of the TLR4-NF-κB-MMP2/MMP9 signaling pathway was examined via Western blot analysis. Limb function was evaluated using the Basso Mouse Scale (BMS) to assess motor function. RESULTS: We observed massive aggregation of neutrophils and the formation of neutrophil extracellular traps (NETs) after spinal cord injury. The use of CD47-blocking antibodies reduced NET formation, mitigated S100A8/A9 production, attenuated BSCB injury, decreased inflammatory cell infiltration, alleviated spinal cord edema, and minimized neuronal death at the site of injury. Furthermore, these antibodies suppressed activation of the TLR4-NF-κB-MMP2/MMP9 signaling pathway. CONCLUSION: The use of CD47-blocking antibodies post-SCI resulted in reduced NET formation. By suppressing the TLR4-NF-κB-MMP2/MMP9 signaling pathway, these antibodies contributed to the preservation of blood-spinal cord barrier (BSCB) integrity, highlighting their potential as a therapeutic strategy for SCI.

Copyright © 2024. Published by Elsevier B.V.

DOI: 10.1016/j.jneuroim.2025.578553 PMID: 39951937 [Indexed for MEDLINE]

Conflict of interest statement: Declaration of competing interest All authors declare that they have no conflict of interest. This work was supported by Tianjin Municipal Health and Wellness Science and Technology Projec. (Grant No. TJWJ2024ZD001)