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Acute injury in the peripheral nervous system triggers an alternative macrophage response

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Ghent researchers on unfolded proteins in inflammatory disease (GROUP-ID)
Project
Ghent researchers on unfolded proteins in inflammatory disease (GROUP-ID)
Abstract
Background: The activation of the immune system in neurodegeneration has detrimental as well as beneficial effects. Which aspects of this immune response aggravate the neurodegenerative breakdown and which stimulate regeneration remains an open question. To unravel the neuroprotective aspects of the immune system we focused on a model of acute peripheral nerve injury, in which the immune system was shown to be protective. Methods: To determine the type of immune response triggered after axotomy of the sciatic nerve, a model for Wallerian degeneration in the peripheral nervous system, we evaluated markers representing the two extremes of a type I and type II immune response (classical vs. alternative) using real-time quantitative polymerase chain reaction (RT-qPCR), western blot, and immunohistochemistry. Results: Our results showed that acute peripheral nerve injury triggers an anti-inflammatory and immunosuppressive response, rather than a pro-inflammatory response. This was reflected by the complete absence of classical macrophage markers (iNOS, IFN gamma, and IL12p40), and the strong up-regulation of tissue repair markers (arginase-1, Ym1, and Trem2). The signal favoring the alternative macrophage environment was induced immediately after nerve damage and appeared to be established within the nerve, well before the infiltration of macrophages. In addition, negative regulators of the innate immune response, as well as the anti-inflammatory cytokine IL-10 were induced. The strict regulation of the immune system dampens the potential tissue damaging effects of an over-activated response. Conclusions: We here demonstrate that acute peripheral nerve injury triggers an inherent protective environment by inducing the M2 phenotype of macrophages and the expression of arginase-1. We believe that the M2 phenotype, associated with a sterile inflammatory response and tissue repair, might explain their neuroprotective capacity. As such, shifting the neurodegeneration-induced immune responses towards an M2/Th2 response could be an important therapeutic strategy.
Keywords
M2, RT-qPCR, Negative regulation, Innate immune system, T-CELLS, UTILIZING IMMUNOHISTOCHEMISTRY, MYELOID CELLS, Neuroprotection, MESSENGER-RNA, NEUROPATHIC PAIN, SPINAL-CORD, Wallerian degeneration, MONOCYTE CHEMOATTRACTANT PROTEIN-1, NECROSIS-FACTOR-ALPHA, WALLERIAN DEGENERATION, AXON REGENERATION

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Citation

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Chicago
Ydens, Elke, Anje Cauwels, Bob Asselbergh, Sofie Goethals, Lieve Peeraer, Guillaume Lornet, Leonardo Almeida-Souza, Jo A Van Ginderachter, Vincent Timmerman, and Sophie Janssens. 2012. “Acute Injury in the Peripheral Nervous System Triggers an Alternative Macrophage Response.” Journal of Neuroinflammation 9.
APA
Ydens, Elke, Cauwels, A., Asselbergh, B., Goethals, S., Peeraer, L., Lornet, G., Almeida-Souza, L., et al. (2012). Acute injury in the peripheral nervous system triggers an alternative macrophage response. JOURNAL OF NEUROINFLAMMATION, 9.
Vancouver
1.
Ydens E, Cauwels A, Asselbergh B, Goethals S, Peeraer L, Lornet G, et al. Acute injury in the peripheral nervous system triggers an alternative macrophage response. JOURNAL OF NEUROINFLAMMATION. 2012;9.
MLA
Ydens, Elke, Anje Cauwels, Bob Asselbergh, et al. “Acute Injury in the Peripheral Nervous System Triggers an Alternative Macrophage Response.” JOURNAL OF NEUROINFLAMMATION 9 (2012): n. pag. Print.
@article{3034203,
  abstract     = {Background: The activation of the immune system in neurodegeneration has detrimental as well as beneficial effects. Which aspects of this immune response aggravate the neurodegenerative breakdown and which stimulate regeneration remains an open question. To unravel the neuroprotective aspects of the immune system we focused on a model of acute peripheral nerve injury, in which the immune system was shown to be protective.
Methods: To determine the type of immune response triggered after axotomy of the sciatic nerve, a model for Wallerian degeneration in the peripheral nervous system, we evaluated markers representing the two extremes of a type I and type II immune response (classical vs. alternative) using real-time quantitative polymerase chain reaction (RT-qPCR), western blot, and immunohistochemistry.
Results: Our results showed that acute peripheral nerve injury triggers an anti-inflammatory and immunosuppressive response, rather than a pro-inflammatory response. This was reflected by the complete absence of classical macrophage markers (iNOS, IFN gamma, and IL12p40), and the strong up-regulation of tissue repair markers (arginase-1, Ym1, and Trem2). The signal favoring the alternative macrophage environment was induced immediately after nerve damage and appeared to be established within the nerve, well before the infiltration of macrophages. In addition, negative regulators of the innate immune response, as well as the anti-inflammatory cytokine IL-10 were induced. The strict regulation of the immune system dampens the potential tissue damaging effects of an over-activated response.
Conclusions: We here demonstrate that acute peripheral nerve injury triggers an inherent protective environment by inducing the M2 phenotype of macrophages and the expression of arginase-1. We believe that the M2 phenotype, associated with a sterile inflammatory response and tissue repair, might explain their neuroprotective capacity. As such, shifting the neurodegeneration-induced immune responses towards an M2/Th2 response could be an important therapeutic strategy.},
  articleno    = {176},
  author       = {Ydens, Elke and Cauwels, Anje and Asselbergh, Bob and Goethals, Sofie and Peeraer, Lieve and Lornet, Guillaume and Almeida-Souza, Leonardo and Van Ginderachter, Jo A and Timmerman, Vincent and Janssens, Sophie},
  issn         = {1742-2094},
  journal      = {JOURNAL OF NEUROINFLAMMATION},
  keywords     = {M2,RT-qPCR,Negative regulation,Innate immune system,T-CELLS,UTILIZING IMMUNOHISTOCHEMISTRY,MYELOID CELLS,Neuroprotection,MESSENGER-RNA,NEUROPATHIC PAIN,SPINAL-CORD,Wallerian degeneration,MONOCYTE CHEMOATTRACTANT PROTEIN-1,NECROSIS-FACTOR-ALPHA,WALLERIAN DEGENERATION,AXON REGENERATION},
  language     = {eng},
  pages        = {17},
  title        = {Acute injury in the peripheral nervous system triggers an alternative macrophage response},
  url          = {http://dx.doi.org/10.1186/1742-2094-9-176},
  volume       = {9},
  year         = {2012},
}

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