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Mechanisms underlying macrophage polarization in spinal cord injury ‐ detrimental and beneficial influences on recovery
Author(s) -
David Samuel
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.210.4
Subject(s) - phagocytosis , microbiology and biotechnology , myelin , macrophage polarization , tumor necrosis factor alpha , downregulation and upregulation , intracellular , cytotoxic t cell , chemistry , spinal cord injury , macrophage , spinal cord , in vitro , immunology , biology , neuroscience , central nervous system , biochemistry , gene
Activated macrophages in the injured CNS can have detrimental and beneficial effects, which may be due to their polarization state. Macrophages can be polarized along a continuum to M1 cells which are pro‐inflammatory and cytotoxic, and M2 cells which are anti‐inflammatory and pro‐repair. Myelin phagocytosis in vitro can induce M1 polarized cells to shift to a M2 phenotype. However, although myelin phagocytosis occurs after spinal cord injury (SCI), macrophages remain predominantly M1 polarized. Our work shows that this failure to switch to a M2 phenotype in vivo after SCI despite on‐going phagocytosis is due in part to TNF. TNF which is upregulated after SCI prevents the myelin phagocytosis induced switch from M1 to M2 polarization. Our work also shows that iron loading of macrophages induces M2 polarized cells to switch to M1 cells and produce TNF. This is important because hemorrhage and cell death after SCI lead to the release of iron. These data indicate that TNF can prevent phagocytosis induced shift of M1 to M2, and increased intracellular iron can promote shift of M2 to M1 phenotype. The combined effect of these influences is detrimental to recovery after SCI.