Cargando…

Crosstalk between macrophages and astrocytes affects proliferation, reactive phenotype and inflammatory response, suggesting a role during reactive gliosis following spinal cord injury

BACKGROUND: Large-scale macrophage infiltration and reactive astrogliosis are hallmarks of early spinal cord injury (SCI) pathology. The exact nature of the macrophage response and relationship between these phenomena have not been explored in detail. Here, we have investigated these responses using...

Descripción completa

Detalles Bibliográficos
Autores principales: Haan, Niels, Zhu, Bangfu, Wang, Jian, Wei, Xiaoqing, Song, Bing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4457974/
https://www.ncbi.nlm.nih.gov/pubmed/26025034
http://dx.doi.org/10.1186/s12974-015-0327-3
_version_ 1782375031872946176
author Haan, Niels
Zhu, Bangfu
Wang, Jian
Wei, Xiaoqing
Song, Bing
author_facet Haan, Niels
Zhu, Bangfu
Wang, Jian
Wei, Xiaoqing
Song, Bing
author_sort Haan, Niels
collection PubMed
description BACKGROUND: Large-scale macrophage infiltration and reactive astrogliosis are hallmarks of early spinal cord injury (SCI) pathology. The exact nature of the macrophage response and relationship between these phenomena have not been explored in detail. Here, we have investigated these responses using a combination of in vivo SCI models, organotypic and primary cultures. METHODS: In vivo macrophage response was investigated using a contusive injury mouse model. Interactions between astrocytes and macrophages were studied in primary or organotypic cultures. Proliferation was assessed though MTT assay and nucleotide incorporation and gene expression changes through qPCR. RESULTS: Seven days following contusive SCI, a mixed M1/M2 macrophage response was seen in the injury site. Conditioned medium from primary M1, but not M2, macrophages are able to induce astrocyte proliferation in both organotypic spinal cord cultures and primary astrocytes. Soluble factors from M1 macrophages induce a reactive astrocyte gene expression pattern, whereas M2 factors inhibit expression of these genes. M2-stimulated astrocytes are also able to decrease both M1 and M2 macrophage proliferation and decrease TNFα production in M1 macrophages. CONCLUSIONS: These results suggest a strong role of M1 macrophages in inducing reactive astrogliosis and the existence of an astrocyte-mediated negative feedback system in order to dampen the immune response. These results, combined with the poor outcomes of the current immunosuppressive steroid treatments in SCI, indicate the need for more targeted therapies, taking into account the significantly different effects of M1 and M2 macrophages, in order to optimise outcome. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12974-015-0327-3) contains supplementary material, which is available to authorized users.
format Online
Article
Text
id pubmed-4457974
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-44579742015-06-07 Crosstalk between macrophages and astrocytes affects proliferation, reactive phenotype and inflammatory response, suggesting a role during reactive gliosis following spinal cord injury Haan, Niels Zhu, Bangfu Wang, Jian Wei, Xiaoqing Song, Bing J Neuroinflammation Research BACKGROUND: Large-scale macrophage infiltration and reactive astrogliosis are hallmarks of early spinal cord injury (SCI) pathology. The exact nature of the macrophage response and relationship between these phenomena have not been explored in detail. Here, we have investigated these responses using a combination of in vivo SCI models, organotypic and primary cultures. METHODS: In vivo macrophage response was investigated using a contusive injury mouse model. Interactions between astrocytes and macrophages were studied in primary or organotypic cultures. Proliferation was assessed though MTT assay and nucleotide incorporation and gene expression changes through qPCR. RESULTS: Seven days following contusive SCI, a mixed M1/M2 macrophage response was seen in the injury site. Conditioned medium from primary M1, but not M2, macrophages are able to induce astrocyte proliferation in both organotypic spinal cord cultures and primary astrocytes. Soluble factors from M1 macrophages induce a reactive astrocyte gene expression pattern, whereas M2 factors inhibit expression of these genes. M2-stimulated astrocytes are also able to decrease both M1 and M2 macrophage proliferation and decrease TNFα production in M1 macrophages. CONCLUSIONS: These results suggest a strong role of M1 macrophages in inducing reactive astrogliosis and the existence of an astrocyte-mediated negative feedback system in order to dampen the immune response. These results, combined with the poor outcomes of the current immunosuppressive steroid treatments in SCI, indicate the need for more targeted therapies, taking into account the significantly different effects of M1 and M2 macrophages, in order to optimise outcome. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12974-015-0327-3) contains supplementary material, which is available to authorized users. BioMed Central 2015-05-30 /pmc/articles/PMC4457974/ /pubmed/26025034 http://dx.doi.org/10.1186/s12974-015-0327-3 Text en © Haan et al. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Haan, Niels
Zhu, Bangfu
Wang, Jian
Wei, Xiaoqing
Song, Bing
Crosstalk between macrophages and astrocytes affects proliferation, reactive phenotype and inflammatory response, suggesting a role during reactive gliosis following spinal cord injury
title Crosstalk between macrophages and astrocytes affects proliferation, reactive phenotype and inflammatory response, suggesting a role during reactive gliosis following spinal cord injury
title_full Crosstalk between macrophages and astrocytes affects proliferation, reactive phenotype and inflammatory response, suggesting a role during reactive gliosis following spinal cord injury
title_fullStr Crosstalk between macrophages and astrocytes affects proliferation, reactive phenotype and inflammatory response, suggesting a role during reactive gliosis following spinal cord injury
title_full_unstemmed Crosstalk between macrophages and astrocytes affects proliferation, reactive phenotype and inflammatory response, suggesting a role during reactive gliosis following spinal cord injury
title_short Crosstalk between macrophages and astrocytes affects proliferation, reactive phenotype and inflammatory response, suggesting a role during reactive gliosis following spinal cord injury
title_sort crosstalk between macrophages and astrocytes affects proliferation, reactive phenotype and inflammatory response, suggesting a role during reactive gliosis following spinal cord injury
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4457974/
https://www.ncbi.nlm.nih.gov/pubmed/26025034
http://dx.doi.org/10.1186/s12974-015-0327-3
work_keys_str_mv AT haanniels crosstalkbetweenmacrophagesandastrocytesaffectsproliferationreactivephenotypeandinflammatoryresponsesuggestingaroleduringreactivegliosisfollowingspinalcordinjury
AT zhubangfu crosstalkbetweenmacrophagesandastrocytesaffectsproliferationreactivephenotypeandinflammatoryresponsesuggestingaroleduringreactivegliosisfollowingspinalcordinjury
AT wangjian crosstalkbetweenmacrophagesandastrocytesaffectsproliferationreactivephenotypeandinflammatoryresponsesuggestingaroleduringreactivegliosisfollowingspinalcordinjury
AT weixiaoqing crosstalkbetweenmacrophagesandastrocytesaffectsproliferationreactivephenotypeandinflammatoryresponsesuggestingaroleduringreactivegliosisfollowingspinalcordinjury
AT songbing crosstalkbetweenmacrophagesandastrocytesaffectsproliferationreactivephenotypeandinflammatoryresponsesuggestingaroleduringreactivegliosisfollowingspinalcordinjury