Macrophage centripetal migration drives spontaneous healing process after spinal cord injury

被引：82

作者：

Kobayakawa, Kazu ^{[1
,2
,3
,4
]}

Ohkawa, Yasuyuki ^{[5
]}

Yoshizaki, Shingo ^{[1
,2
]}

Tamaru, Tetsuya ^{[1
,2
]}

Saito, Takeyuki ^{[2
]}

Kijima, Ken ^{[1
,2
]}

Yokota, Kazuya ^{[2
]}

Hara, Masamitsu ^{[2
,3
]}

Kubota, Kensuke ^{[2
,4
]}

Matsumoto, Yoshihiro ^{[2
]}

Harimaya, Katsumi ^{[2
]}

Ozato, Keiko ^{[6
]}

Masuda, Takahiro ^{[7
]}

Tsuda, Makoto ^{[8
]}

Tamura, Tomohiko ^{[9
]}

Inoue, Kazuhide ^{[7
]}

Edgerton, V. Reggie ^{[3
,4
]}

Iwamoto, Yukihide ^{[10
]}

Nakashima, Yasuharu ^{[2
]}

Okada, Seiji ^{[1
]}

机构：

[1] Kyushu Univ, Med Inst Bioregulat, Dept Immunobiol & Neurosci, Fukuoka, Fukuoka, Japan

[2] Kyushu Univ, Grad Sch Med Sci, Department Orthoped Surg, Fukuoka, Fukuoka, Japan

[3] Univ Calif Los Angeles, Dept Integrat Biol & Physiol, Los Angeles, CA USA

[4] Spinal Injuries Ctr, Dept Orthoped Surg, Iizuka, Fukuoka, Japan

[5] Kyushu Univ, Med Inst Bioregulat, Div Transcript, Fukuoka, Fukuoka, Japan

[6] NICHD, Program Genom Differentiat, NIH, Bethesda, MD USA

[7] Kyushu Univ, Grad Sch Pharmaceut Sci, Dept Mol & Syst Pharmacol, Fukuoka, Fukuoka, Japan

[8] Kyushu Univ, Grad Sch Pharmaceut Sci, Dept Life Innovat, Fukuoka, Fukuoka, Japan

[9] Yokohama City Univ, Grad Sch Med, Dept Immunol, Yokohama, Kanagawa, Japan

[10] Kyushu Rosai Hosp, Kitakyushu, Fukuoka, Japan

来源：

SCIENCE ADVANCES | 2019年 / 5卷 / 05期

关键词：

TRANSCRIPTION FACTOR; AXONAL DIEBACK; INFLAMMATORY RESPONSE; INTERFERON-GAMMA; CROSS-TALK; RNA-SEQ; CELLS; RECRUITMENT; COMPLEMENT; RECOVERY;

D O I：

10.1126/sciadv.aav5086

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：14

共 66 条

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