Macrophage centripetal migration drives spontaneous healing process after spinal cord injury
| العنوان: | Macrophage centripetal migration drives spontaneous healing process after spinal cord injury |
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| المؤلفون: | Katsumi Harimaya, Kazu Kobayakawa, Ken Kijima, Takahiro Masuda, V. Reggie Edgerton, Yukihide Iwamoto, Yoshihiro Matsumoto, Kensuke Kubota, Tomohiko Tamura, Yasuharu Nakashima, Masamitsu Hara, Keiko Ozato, Takeyuki Saito, Yasuyuki Ohkawa, Makoto Tsuda, Kazuya Yokota, Seiji Okada, Tetsuya Tamaru, Kazuhide Inoue, Shingo Yoshizaki |
| المصدر: | Science Advances Science advances, vol 5, iss 5 |
| بيانات النشر: | American Association for the Advancement of Science, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Neutrophils, Axonal loss, Diseases and Disorders, Neurodegenerative, Inbred C57BL, Regenerative Medicine, Transgenic, Mice, 0302 clinical medicine, Injury - Trauma - (Head and Spine), Cell Movement, Macrophage, 2.1 Biological and endogenous factors, Aetiology, Spinal Cord Injury, Spinal cord injury, Research Articles, Neurons, 0303 health sciences, Multidisciplinary, Purinergic receptor, Brain, SciAdv r-articles, CD, medicine.anatomical_structure, Differentiation, Interferon Regulatory Factors, Female, Microglia, Research Article, Cord, Central nervous system, Antigens, Differentiation, Myelomonocytic, Mice, Transgenic, Complement C5a, 03 medical and health sciences, Antigens, CD, medicine, Animals, Remyelination, Antigens, Spinal Cord Injuries, 030304 developmental biology, business.industry, Animal, Macrophages, Neurosciences, Myelomonocytic, Spinal cord, medicine.disease, Axons, Nerve Regeneration, Mice, Inbred C57BL, Disease Models, Animal, Astrocytes, Cellular Neuroscience, Disease Models, Injury (total) Accidents/Adverse Effects, business, Neuroscience, 030217 neurology & neurosurgery |
| الوصف: | Migration of macrophages via IRF8 toward a core lesion is important for the spontaneous recovery after spinal cord injury. 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. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2375-2548 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3ce33c9b711d26160b4137fe7703f5d0 http://europepmc.org/articles/PMC6520026 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....3ce33c9b711d26160b4137fe7703f5d0 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 23752548 |
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