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Tissue-resident M2 macrophages directly contact primary sensory neurons in the sensory ganglia after nerve injury

BACKGROUND: Macrophages in the peripheral nervous system are key players in the repair of nerve tissue and the development of neuropathic pain due to peripheral nerve injury. However, there is a lack of information on the origin and morphological features of macrophages in sensory ganglia after peri...

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Autores principales: Iwai, Haruki, Ataka, Koji, Suzuki, Hajime, Dhar, Ashis, Kuramoto, Eriko, Yamanaka, Atsushi, Goto, Tetsuya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8513227/
https://www.ncbi.nlm.nih.gov/pubmed/34645458
http://dx.doi.org/10.1186/s12974-021-02283-z
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author Iwai, Haruki
Ataka, Koji
Suzuki, Hajime
Dhar, Ashis
Kuramoto, Eriko
Yamanaka, Atsushi
Goto, Tetsuya
author_facet Iwai, Haruki
Ataka, Koji
Suzuki, Hajime
Dhar, Ashis
Kuramoto, Eriko
Yamanaka, Atsushi
Goto, Tetsuya
author_sort Iwai, Haruki
collection PubMed
description BACKGROUND: Macrophages in the peripheral nervous system are key players in the repair of nerve tissue and the development of neuropathic pain due to peripheral nerve injury. However, there is a lack of information on the origin and morphological features of macrophages in sensory ganglia after peripheral nerve injury, unlike those in the brain and spinal cord. We analyzed the origin and morphological features of sensory ganglionic macrophages after nerve ligation or transection using wild-type mice and mice with bone-marrow cell transplants. METHODS: After protecting the head of C57BL/6J mice with lead caps, they were irradiated and transplanted with bone-marrow-derived cells from GFP transgenic mice. The infraorbital nerve of a branch of the trigeminal nerve of wild-type mice was ligated or the infraorbital nerve of GFP-positive bone-marrow-cell-transplanted mice was transected. After immunostaining the trigeminal ganglion, the structures of the ganglionic macrophages, neurons, and satellite glial cells were analyzed using two-dimensional or three-dimensional images. RESULTS: The number of damaged neurons in the trigeminal ganglion increased from day 1 after infraorbital nerve ligation. Ganglionic macrophages proliferated from days 3 to 5. Furthermore, the numbers of macrophages increased from days 3 to 15. Bone-marrow-derived macrophages increased on day 7 after the infraorbital nerve was transected in the trigeminal ganglion of GFP-positive bone-marrow-cell-transplanted mice but most of the ganglionic macrophages were composed of tissue-resident cells. On day 7 after infraorbital nerve ligation, ganglionic macrophages increased in volume, extended their processes between the neurons and satellite glial cells, and contacted these neurons. Most of the ganglionic macrophages showed an M2 phenotype when contact was observed, and little neuronal cell death occurred. CONCLUSION: Most of the macrophages that appear after a nerve injury are tissue-resident, and these make direct contact with damaged neurons that act in a tissue-protective manner in the M2 phenotype. These results imply that tissue-resident macrophages signal to neurons directly through physical contact. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12974-021-02283-z.
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spelling pubmed-85132272021-10-20 Tissue-resident M2 macrophages directly contact primary sensory neurons in the sensory ganglia after nerve injury Iwai, Haruki Ataka, Koji Suzuki, Hajime Dhar, Ashis Kuramoto, Eriko Yamanaka, Atsushi Goto, Tetsuya J Neuroinflammation Research BACKGROUND: Macrophages in the peripheral nervous system are key players in the repair of nerve tissue and the development of neuropathic pain due to peripheral nerve injury. However, there is a lack of information on the origin and morphological features of macrophages in sensory ganglia after peripheral nerve injury, unlike those in the brain and spinal cord. We analyzed the origin and morphological features of sensory ganglionic macrophages after nerve ligation or transection using wild-type mice and mice with bone-marrow cell transplants. METHODS: After protecting the head of C57BL/6J mice with lead caps, they were irradiated and transplanted with bone-marrow-derived cells from GFP transgenic mice. The infraorbital nerve of a branch of the trigeminal nerve of wild-type mice was ligated or the infraorbital nerve of GFP-positive bone-marrow-cell-transplanted mice was transected. After immunostaining the trigeminal ganglion, the structures of the ganglionic macrophages, neurons, and satellite glial cells were analyzed using two-dimensional or three-dimensional images. RESULTS: The number of damaged neurons in the trigeminal ganglion increased from day 1 after infraorbital nerve ligation. Ganglionic macrophages proliferated from days 3 to 5. Furthermore, the numbers of macrophages increased from days 3 to 15. Bone-marrow-derived macrophages increased on day 7 after the infraorbital nerve was transected in the trigeminal ganglion of GFP-positive bone-marrow-cell-transplanted mice but most of the ganglionic macrophages were composed of tissue-resident cells. On day 7 after infraorbital nerve ligation, ganglionic macrophages increased in volume, extended their processes between the neurons and satellite glial cells, and contacted these neurons. Most of the ganglionic macrophages showed an M2 phenotype when contact was observed, and little neuronal cell death occurred. CONCLUSION: Most of the macrophages that appear after a nerve injury are tissue-resident, and these make direct contact with damaged neurons that act in a tissue-protective manner in the M2 phenotype. These results imply that tissue-resident macrophages signal to neurons directly through physical contact. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12974-021-02283-z. BioMed Central 2021-10-13 /pmc/articles/PMC8513227/ /pubmed/34645458 http://dx.doi.org/10.1186/s12974-021-02283-z Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Iwai, Haruki
Ataka, Koji
Suzuki, Hajime
Dhar, Ashis
Kuramoto, Eriko
Yamanaka, Atsushi
Goto, Tetsuya
Tissue-resident M2 macrophages directly contact primary sensory neurons in the sensory ganglia after nerve injury
title Tissue-resident M2 macrophages directly contact primary sensory neurons in the sensory ganglia after nerve injury
title_full Tissue-resident M2 macrophages directly contact primary sensory neurons in the sensory ganglia after nerve injury
title_fullStr Tissue-resident M2 macrophages directly contact primary sensory neurons in the sensory ganglia after nerve injury
title_full_unstemmed Tissue-resident M2 macrophages directly contact primary sensory neurons in the sensory ganglia after nerve injury
title_short Tissue-resident M2 macrophages directly contact primary sensory neurons in the sensory ganglia after nerve injury
title_sort tissue-resident m2 macrophages directly contact primary sensory neurons in the sensory ganglia after nerve injury
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8513227/
https://www.ncbi.nlm.nih.gov/pubmed/34645458
http://dx.doi.org/10.1186/s12974-021-02283-z
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