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, Tsuda Makoto, Tomohiko Tamura, Kazuhide Inoue, V. Reggie Edgerton, Yukihide Iwamoto, Yasuharu Nakashima, Seiji Okada

研究成果: ジャーナルへの寄稿記事

抄録

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.

元の言語英語
記事番号eaav5086
ジャーナルScience Advances
5
発行部数5
DOI
出版物ステータス出版済み - 5 15 2019

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

All Science Journal Classification (ASJC) codes

  • General
  • Physics and Astronomy (miscellaneous)

これを引用

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; Makoto, Tsuda; Tamura, Tomohiko; Inoue, Kazuhide; Reggie Edgerton, V.; Iwamoto, Yukihide; Nakashima, Yasuharu; Okada, Seiji.

:: Science Advances, 巻 5, 番号 5, eaav5086, 15.05.2019.

研究成果: ジャーナルへの寄稿記事

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, Makoto, T, 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, 巻. 5, 番号 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 ; Makoto, Tsuda ; Tamura, Tomohiko ; Inoue, Kazuhide ; Reggie Edgerton, V. ; Iwamoto, Yukihide ; Nakashima, Yasuharu ; Okada, Seiji. / Macrophage centripetal migration drives spontaneous healing process after spinal cord injury. :: Science Advances. 2019 ; 巻 5, 番号 5.
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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.",
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