Complement Protein C3 Suppresses Axon Growth and Promotes Neuron Loss

Abstract 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 cle...

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Autores principales:	Sheri L. Peterson, Hal X. Nguyen, Oscar A. Mendez, Aileen J. Anderson
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f77d46d4add041179bd71265ab11ab96
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spelling	oai:doaj.org-article:f77d46d4add041179bd71265ab11ab962021-12-02T15:05:37ZComplement Protein C3 Suppresses Axon Growth and Promotes Neuron Loss10.1038/s41598-017-11410-x2045-2322https://doaj.org/article/f77d46d4add041179bd71265ab11ab962017-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-11410-xhttps://doaj.org/toc/2045-2322Abstract 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.Sheri L. PetersonHal X. NguyenOscar A. MendezAileen J. AndersonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sheri L. Peterson Hal X. Nguyen Oscar A. Mendez Aileen J. Anderson Complement Protein C3 Suppresses Axon Growth and Promotes Neuron Loss
description	Abstract 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	article
author	Sheri L. Peterson Hal X. Nguyen Oscar A. Mendez Aileen J. Anderson
author_facet	Sheri L. Peterson Hal X. Nguyen Oscar A. Mendez Aileen J. Anderson
author_sort	Sheri L. Peterson
title	Complement Protein C3 Suppresses Axon Growth and Promotes Neuron Loss
title_short	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_sort	complement protein c3 suppresses axon growth and promotes neuron loss
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/f77d46d4add041179bd71265ab11ab96
work_keys_str_mv	AT sherilpeterson complementproteinc3suppressesaxongrowthandpromotesneuronloss AT halxnguyen complementproteinc3suppressesaxongrowthandpromotesneuronloss AT oscaramendez complementproteinc3suppressesaxongrowthandpromotesneuronloss AT aileenjanderson complementproteinc3suppressesaxongrowthandpromotesneuronloss
_version_	1718388806021808128

Complement Protein C3 Suppresses Axon Growth and Promotes Neuron Loss

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