Journal article
Infiltrating Blood-Derived Macrophages Are Vital Cells Playing an Anti-inflammatory Role in Recovery from Spinal Cord Injury in Mice
PLoS Medicine, Vol.6(7)
Jul/2009
Abstract
Background: Although macrophages (M Phi) are known as essential players in wound healing, their contribution to recovery from spinal cord injury (SCI) is a subject of debate. The difficulties in distinguishing between different M Phi subpopulations at the lesion site have further contributed to the controversy and led to the common view of M Phi as functionally homogenous. Given the massive accumulation in the injured spinal cord of activated resident microglia, which are the native immune occupants of the central nervous system (CNS), the recruitment of additional infiltrating monocytes from the peripheral blood seems puzzling. A key question that remains is whether the infiltrating monocyte-derived M Phi contribute to repair, or represent an unavoidable detrimental response. The hypothesis of the current study is that a specific population of infiltrating monocyte-derived M Phi is functionally distinct from the inflammatory resident microglia and is essential for recovery from SCI. Methods and Findings: We inflicted SCI in adult mice, and tested the effect of infiltrating monocyte-derived M Phi on the recovery process. Adoptive transfer experiments and bone marrow chimeras were used to functionally distinguish between the resident microglia and the infiltrating monocyte-derived M Phi. We followed the infiltration of the monocyte-derived M Phi to the injured site and characterized their spatial distribution and phenotype. Increasing the naive monocyte pool by either adoptive transfer or CNS-specific vaccination resulted in a higher number of spontaneously recruited cells and improved recovery. Selective ablation of infiltrating monocyte-derived M Phi following SCI while sparing the resident microglia, using either antibody-mediated depletion or conditional ablation by diphtheria toxin, impaired recovery. Reconstitution of the peripheral blood with monocytes resistant to ablation restored the lost motor functions. Importantly, the infiltrating monocyte-derived M
Details
- Title
- Infiltrating Blood-Derived Macrophages Are Vital Cells Playing an Anti-inflammatory Role in Recovery from Spinal Cord Injury in Mice
- Creators
- Ravid Shechter (null) - 972WIS_INST___123Anat London (null)Chen Varol (null)Catarina Raposo (null)Melania Cusimano (null)Gili Yovel (null) - The Weizmann Institute of ScienceAsya Rolls (null)Matthias Mack (null)Stefano Pluchino (null)Gianvito Martino (null)Steffen Jung (null) - 972WIS_INST___120Michal Schwartz (null) - 972WIS_INST___123
- Resource Type
- Journal article
- Publication Details
- PLoS Medicine, Vol.6(7); Jul/2009
- Number of pages
- 17
- Language
- English
- DOI
- https://doi.org/10.1371/journal.pmed.1000113
- Grant note
- High Q Foundation; NRSAD award; ERC award; IsrALS; Israel Science Foundation; MINERVA Foundation; ISF Bio-Med research grantMS holds the Maurice and Ilse Katz Professorial Chair in Neuroimmunology. The work was supported in part by the High Q Foundation, an NRSAD award, ERC award, and by IsrALS, given to MS. This work was supported also by the Israel Science Foundation, given to MS and SJ. SJ was supported by the MINERVA Foundation and by a joint ISF Bio-Med research grant, and is the incumbent of the Pauline Recanati Career Development Chair. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript._ALMAME_DELIMITER_
- Record Identifier
- 993261829403596
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