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Complement Protein C3 Suppresses Axon Growth and Promotes Neuron Loss
The inflammatory response to spinal cord injury (SCI) involves localization and activation of innate and adaptive immune cells and proteins, including the complement cascade. Complement C3 is important for the classical, alternative, and lectin pathways of complement activation, and its cleavage pro...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5635131/ https://www.ncbi.nlm.nih.gov/pubmed/29018286 http://dx.doi.org/10.1038/s41598-017-11410-x |
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author | Peterson, Sheri L. Nguyen, Hal X. Mendez, Oscar A. Anderson, Aileen J. |
author_facet | Peterson, Sheri L. Nguyen, Hal X. Mendez, Oscar A. Anderson, Aileen J. |
author_sort | Peterson, Sheri L. |
collection | PubMed |
description | The inflammatory response to spinal cord injury (SCI) involves localization and activation of innate and adaptive immune cells and proteins, including the complement cascade. Complement C3 is important for the classical, alternative, and lectin pathways of complement activation, and its cleavage products C3a and C3b mediate several functions in the context of inflammation, but little is known about the potential functions of C3 on regeneration and survival of injured neurons after SCI. We report that 6 weeks after dorsal hemisection with peripheral conditioning lesion, C3(−/−) mice demonstrated a 2-fold increase in sensory axon regeneration in the spinal cord in comparison to wildtype C3(+/+) mice. In vitro, addition of C3 tripled both myelin-mediated neurite outgrowth inhibition and neuron loss versus myelin alone, and ELISA experiments revealed that myelin serine proteases cleave C3 to generate active fragments. Addition of purified C3 cleavage products to cultured neurons suggested that C3b is responsible for the growth inhibitory and neurotoxic or anti-adhesion activities of C3. These data indicate that C3 reduces neurite outgrowth and neuronal viability in vitro and restricts axon regeneration in vivo, and demonstrate a novel, non-traditional role for this inflammatory protein in the central nervous system. |
format | Online Article Text |
id | pubmed-5635131 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-56351312017-10-18 Complement Protein C3 Suppresses Axon Growth and Promotes Neuron Loss Peterson, Sheri L. Nguyen, Hal X. Mendez, Oscar A. Anderson, Aileen J. Sci Rep Article The inflammatory response to spinal cord injury (SCI) involves localization and activation of innate and adaptive immune cells and proteins, including the complement cascade. Complement C3 is important for the classical, alternative, and lectin pathways of complement activation, and its cleavage products C3a and C3b mediate several functions in the context of inflammation, but little is known about the potential functions of C3 on regeneration and survival of injured neurons after SCI. We report that 6 weeks after dorsal hemisection with peripheral conditioning lesion, C3(−/−) mice demonstrated a 2-fold increase in sensory axon regeneration in the spinal cord in comparison to wildtype C3(+/+) mice. In vitro, addition of C3 tripled both myelin-mediated neurite outgrowth inhibition and neuron loss versus myelin alone, and ELISA experiments revealed that myelin serine proteases cleave C3 to generate active fragments. Addition of purified C3 cleavage products to cultured neurons suggested that C3b is responsible for the growth inhibitory and neurotoxic or anti-adhesion activities of C3. These data indicate that C3 reduces neurite outgrowth and neuronal viability in vitro and restricts axon regeneration in vivo, and demonstrate a novel, non-traditional role for this inflammatory protein in the central nervous system. Nature Publishing Group UK 2017-10-10 /pmc/articles/PMC5635131/ /pubmed/29018286 http://dx.doi.org/10.1038/s41598-017-11410-x Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Peterson, Sheri L. Nguyen, Hal X. Mendez, Oscar A. Anderson, Aileen J. Complement Protein C3 Suppresses Axon Growth and Promotes Neuron Loss |
title | Complement Protein C3 Suppresses Axon Growth and Promotes Neuron Loss |
title_full | Complement Protein C3 Suppresses Axon Growth and Promotes Neuron Loss |
title_fullStr | Complement Protein C3 Suppresses Axon Growth and Promotes Neuron Loss |
title_full_unstemmed | Complement Protein C3 Suppresses Axon Growth and Promotes Neuron Loss |
title_short | Complement Protein C3 Suppresses Axon Growth and Promotes Neuron Loss |
title_sort | complement protein c3 suppresses axon growth and promotes neuron loss |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5635131/ https://www.ncbi.nlm.nih.gov/pubmed/29018286 http://dx.doi.org/10.1038/s41598-017-11410-x |
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