Macrophage centripetal migration drives spontaneous healing process after spinal cord injury

Kazu Kobayakawa, Yasuyuki Ohkawa, Shingo Yoshizaki, Tetsuya Tamaru, Takeyuki Saito, Ken Kijima, Kazuya Yokota, Masamitsu Hara, Kensuke Kubota, Yoshihiro Matsumoto, Katsumi Harimaya, Keiko Ozato, Takahiro Masuda, Makoto Tsuda, Tomohiko Tamura, Kazuhide Inoue, V. Reggie Edgerton, Yukihide Iwamoto, Yasuharu Nakashima, Seiji Okada

Research output: Contribution to journalArticle

Abstract

Traumatic spinal cord injury (SCI) brings numerous inflammatory cells, including macrophages, from the circulating blood to lesions, but pathophysiological impact resulting from spatiotemporal dynamics of macrophages is unknown. Here, we show that macrophages centripetally migrate toward the lesion epicenter after infiltrating into the wide range of spinal cord, depending on the gradient of chemoattractant C5a. However, macrophages lacking interferon regulatory factor 8 (IRF8) cannot migrate toward the epicenter and remain widely scattered in the injured cord with profound axonal loss and little remyelination, resulting in a poor functional outcome after SCI. Time-lapse imaging and P2X/YRs blockade revealed that macrophage migration via IRF8 was caused by purinergic receptors involved in the C5a-directed migration. Conversely, pharmacological promotion of IRF8 activation facilitated macrophage centripetal movement, thereby improving the SCI recovery. Our findings reveal the importance of macrophage centripetal migration via IRF8, providing a novel therapeutic target for central nervous system injury.

Original languageEnglish
Article numbereaav5086
JournalScience Advances
Volume5
Issue number5
DOIs
Publication statusPublished - May 15 2019

Fingerprint

spinal cord injuries
macrophages
healing
interferon
lesions
spinal cord
central nervous system
promotion
blood
recovery
activation
gradients

All Science Journal Classification (ASJC) codes

  • Physics and Astronomy (miscellaneous)
  • General

Cite this

Macrophage centripetal migration drives spontaneous healing process after spinal cord injury. / Kobayakawa, Kazu; Ohkawa, Yasuyuki; Yoshizaki, Shingo; Tamaru, Tetsuya; Saito, Takeyuki; Kijima, Ken; Yokota, Kazuya; Hara, Masamitsu; Kubota, Kensuke; Matsumoto, Yoshihiro; Harimaya, Katsumi; Ozato, Keiko; Masuda, Takahiro; Tsuda, Makoto; Tamura, Tomohiko; Inoue, Kazuhide; Reggie Edgerton, V.; Iwamoto, Yukihide; Nakashima, Yasuharu; Okada, Seiji.

In: Science Advances, Vol. 5, No. 5, eaav5086, 15.05.2019.

Research output: Contribution to journalArticle

Kobayakawa, K, Ohkawa, Y, Yoshizaki, S, Tamaru, T, Saito, T, Kijima, K, Yokota, K, Hara, M, Kubota, K, Matsumoto, Y, Harimaya, K, Ozato, K, Masuda, T, Tsuda, M, Tamura, T, Inoue, K, Reggie Edgerton, V, Iwamoto, Y, Nakashima, Y & Okada, S 2019, 'Macrophage centripetal migration drives spontaneous healing process after spinal cord injury', Science Advances, vol. 5, no. 5, eaav5086. https://doi.org/10.1126/sciadv.aav5086
Kobayakawa, Kazu ; Ohkawa, Yasuyuki ; Yoshizaki, Shingo ; Tamaru, Tetsuya ; Saito, Takeyuki ; Kijima, Ken ; Yokota, Kazuya ; Hara, Masamitsu ; Kubota, Kensuke ; Matsumoto, Yoshihiro ; Harimaya, Katsumi ; Ozato, Keiko ; Masuda, Takahiro ; Tsuda, Makoto ; Tamura, Tomohiko ; Inoue, Kazuhide ; Reggie Edgerton, V. ; Iwamoto, Yukihide ; Nakashima, Yasuharu ; Okada, Seiji. / Macrophage centripetal migration drives spontaneous healing process after spinal cord injury. In: Science Advances. 2019 ; Vol. 5, No. 5.
@article{945d9d2410a04c14accd1e53528ccc3c,
title = "Macrophage centripetal migration drives spontaneous healing process after spinal cord injury",
abstract = "Traumatic spinal cord injury (SCI) brings numerous inflammatory cells, including macrophages, from the circulating blood to lesions, but pathophysiological impact resulting from spatiotemporal dynamics of macrophages is unknown. Here, we show that macrophages centripetally migrate toward the lesion epicenter after infiltrating into the wide range of spinal cord, depending on the gradient of chemoattractant C5a. However, macrophages lacking interferon regulatory factor 8 (IRF8) cannot migrate toward the epicenter and remain widely scattered in the injured cord with profound axonal loss and little remyelination, resulting in a poor functional outcome after SCI. Time-lapse imaging and P2X/YRs blockade revealed that macrophage migration via IRF8 was caused by purinergic receptors involved in the C5a-directed migration. Conversely, pharmacological promotion of IRF8 activation facilitated macrophage centripetal movement, thereby improving the SCI recovery. Our findings reveal the importance of macrophage centripetal migration via IRF8, providing a novel therapeutic target for central nervous system injury.",
author = "Kazu Kobayakawa and Yasuyuki Ohkawa and Shingo Yoshizaki and Tetsuya Tamaru and Takeyuki Saito and Ken Kijima and Kazuya Yokota and Masamitsu Hara and Kensuke Kubota and Yoshihiro Matsumoto and Katsumi Harimaya and Keiko Ozato and Takahiro Masuda and Makoto Tsuda and Tomohiko Tamura and Kazuhide Inoue and {Reggie Edgerton}, V. and Yukihide Iwamoto and Yasuharu Nakashima and Seiji Okada",
year = "2019",
month = "5",
day = "15",
doi = "10.1126/sciadv.aav5086",
language = "English",
volume = "5",
journal = "Indian Journal of Pure and Applied Physics",
issn = "0019-5596",
publisher = "National Institute of Science Communication and Information Resources (NISCAIR)",
number = "5",

}

TY - JOUR

T1 - Macrophage centripetal migration drives spontaneous healing process after spinal cord injury

AU - Kobayakawa, Kazu

AU - Ohkawa, Yasuyuki

AU - Yoshizaki, Shingo

AU - Tamaru, Tetsuya

AU - Saito, Takeyuki

AU - Kijima, Ken

AU - Yokota, Kazuya

AU - Hara, Masamitsu

AU - Kubota, Kensuke

AU - Matsumoto, Yoshihiro

AU - Harimaya, Katsumi

AU - Ozato, Keiko

AU - Masuda, Takahiro

AU - Tsuda, Makoto

AU - Tamura, Tomohiko

AU - Inoue, Kazuhide

AU - Reggie Edgerton, V.

AU - Iwamoto, Yukihide

AU - Nakashima, Yasuharu

AU - Okada, Seiji

PY - 2019/5/15

Y1 - 2019/5/15

N2 - Traumatic spinal cord injury (SCI) brings numerous inflammatory cells, including macrophages, from the circulating blood to lesions, but pathophysiological impact resulting from spatiotemporal dynamics of macrophages is unknown. Here, we show that macrophages centripetally migrate toward the lesion epicenter after infiltrating into the wide range of spinal cord, depending on the gradient of chemoattractant C5a. However, macrophages lacking interferon regulatory factor 8 (IRF8) cannot migrate toward the epicenter and remain widely scattered in the injured cord with profound axonal loss and little remyelination, resulting in a poor functional outcome after SCI. Time-lapse imaging and P2X/YRs blockade revealed that macrophage migration via IRF8 was caused by purinergic receptors involved in the C5a-directed migration. Conversely, pharmacological promotion of IRF8 activation facilitated macrophage centripetal movement, thereby improving the SCI recovery. Our findings reveal the importance of macrophage centripetal migration via IRF8, providing a novel therapeutic target for central nervous system injury.

AB - Traumatic spinal cord injury (SCI) brings numerous inflammatory cells, including macrophages, from the circulating blood to lesions, but pathophysiological impact resulting from spatiotemporal dynamics of macrophages is unknown. Here, we show that macrophages centripetally migrate toward the lesion epicenter after infiltrating into the wide range of spinal cord, depending on the gradient of chemoattractant C5a. However, macrophages lacking interferon regulatory factor 8 (IRF8) cannot migrate toward the epicenter and remain widely scattered in the injured cord with profound axonal loss and little remyelination, resulting in a poor functional outcome after SCI. Time-lapse imaging and P2X/YRs blockade revealed that macrophage migration via IRF8 was caused by purinergic receptors involved in the C5a-directed migration. Conversely, pharmacological promotion of IRF8 activation facilitated macrophage centripetal movement, thereby improving the SCI recovery. Our findings reveal the importance of macrophage centripetal migration via IRF8, providing a novel therapeutic target for central nervous system injury.

UR - http://www.scopus.com/inward/record.url?scp=85065865262&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85065865262&partnerID=8YFLogxK

U2 - 10.1126/sciadv.aav5086

DO - 10.1126/sciadv.aav5086

M3 - Article

C2 - 31106270

AN - SCOPUS:85065865262

VL - 5

JO - Indian Journal of Pure and Applied Physics

JF - Indian Journal of Pure and Applied Physics

SN - 0019-5596

IS - 5

M1 - eaav5086

ER -