Identification of Two Distinct Macrophage Subsets with Divergent Effects Causing either Neurotoxicity or Regeneration in the Injured Mouse Spinal Cord

Journal of Neuroscience - Tập 29 Số 43 - Trang 13435-13444 - 2009
Kristina A. Kigerl1,2, John C. Gensel1,2, Daniel P. Ankeny1,2, Jessica Alexander1,3, Dustin J. Donnelly1,4, Phillip G. Popovich1,2,4,3
1Center for Brain and Spinal Cord Repair,
2Department of Molecular Virology, Immunology, and Medical Genetics
3Neuroscience Graduate Studies Program, and
4Medical Scientist Program, The Ohio State University, Columbus, Ohio 43210

Tóm tắt

Macrophages dominate sites of CNS injury in which they promote both injury and repair. These divergent effects may be caused by distinct macrophage subsets, i.e., “classically activated” proinflammatory (M1) or “alternatively activated” anti-inflammatory (M2) cells. Here, we show that an M1 macrophage response is rapidly induced and then maintained at sites of traumatic spinal cord injury and that this response overwhelms a comparatively smaller and transient M2 macrophage response. The high M1/M2 macrophage ratio has significant implications for CNS repair. Indeed, we present novel data showing that only M1 macrophages are neurotoxic and M2 macrophages promote a regenerative growth response in adult sensory axons, even in the context of inhibitory substrates that dominate sites of CNS injury (e.g., proteoglycans and myelin). Together, these data suggest that polarizing the differentiation of resident microglia and infiltrating blood monocytes toward an M2 or “alternatively” activated macrophage phenotype could promote CNS repair while limiting secondary inflammatory-mediated injury.

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Journal of Neuroscience

Tập 29 Số 43

13435-13444

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