Author:
Ono Gentaro,Kobayakawa Kazu,Saiwai Hirokazu,Tamaru Tetsuya,Iura Hirotaka,Haruta Yohei,Kitade Kazuki,Iida Keiichiro,Kawaguchi Kenichi,Matsumoto Yoshihiro,Tsuda Makoto,Tamura Tomohiko,Ozato Keiko,Inoue Kazuhide,Konno Dai-Jiro,Maeda Takeshi,Okada Seiji,Nakashima Yasuharu
Abstract
AbstractAfter spinal cord injury (SCI), inflammatory cells such as macrophages infiltrate the injured area, and astrocytes migrate, forming a glial scar around macrophages. The glial scar inhibits axonal regeneration, resulting in significant permanent disability. However, the mechanism through which glial scar-forming astrocytes migrate to the injury site has not been clarified. Here we show that migrating macrophages attract reactive astrocytes toward the center of the lesion after SCI. Chimeric mice with bone marrow lacking IRF8, which controls macrophage centripetal migration after SCI, showed widely scattered macrophages in the injured spinal cord with the formation of a huge glial scar around the macrophages. To determine whether astrocytes or macrophages play a leading role in determining the directions of migration, we generated chimeric mice with reactive astrocyte-specific Socs3−/− mice, which showed enhanced astrocyte migration, and bone marrow from IRF8−/− mice. In this mouse model, macrophages were widely scattered, and a huge glial scar was formed around the macrophages as in wild-type mice that were transplanted with IRF8−/− bone marrow. In addition, we revealed that macrophage-secreted ATP-derived ADP attracts astrocytes via the P2Y1 receptor. Our findings revealed a mechanism through which migrating macrophages attract astrocytes and affect the pathophysiology and outcome after SCI.
Funder
Japan Society for the Promotion of Science
ZENKYOREN
Takeda Science Foundation
JST FOREST Program
Publisher
Springer Science and Business Media LLC
Cited by
1 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献