https://scholars.lib.ntu.edu.tw/handle/123456789/416517
標題: | Erythrocyte efferocytosis modulates macrophages towards recovery after intracerebral hemorrhage | 作者: | Che-Feng Chang Goods, B.A. Askenase, M.H. Hammond, M.D. Renfroe, S.C. Steinschneider, A.F. Landreneau, M.J. Ai, Y. Beatty, H.E. Da Costa, L.H.A. Mack, M. Sheth, K.N. Greer, D.M. Huttner, A. Coman, D. Hyder, F. Ghosh, S. Rothlin, C.V. Christopher Love, J. Sansing, L.H. |
公開日期: | 2018 | 出版社: | AMER SOC CLINICAL INVESTIGATION INC | 卷: | 128 | 期: | 2 | 起(迄)頁: | 607 | 來源出版物: | Journal of Clinical Investigation | 摘要: | Macrophages are a source of both proinflammatory and restorative functions in damaged tissue through complex dynamic phenotypic changes. Here, we sought to determine whether monocyte-derived macrophages (MDMs) contribute to recovery after acute sterile brain injury. By profiling the transcriptional dynamics of MDMs in the murine brain after experimental intracerebral hemorrhage (ICH), we found robust phenotypic changes in the infiltrating MDMs over time and demonstrated that MDMs are essential for optimal hematoma clearance and neurological recovery. Next, we identified the mechanism by which the engulfment of erythrocytes with exposed phosphatidylserine directly modulated the phenotype of both murine and human MDMs. In mice, loss of receptor tyrosine kinases AXL and MERTK reduced efferocytosis of eryptotic erythrocytes and hematoma clearance, worsened neurological recovery, exacerbated iron deposition, and decreased alternative activation of macrophages after ICH. Patients with higher circulating soluble AXL had poor 1-year outcomes after ICH onset, suggesting that therapeutically augmenting efferocytosis May improve functional outcomes by both reducing tissue injury and promoting the development of reparative macrophage responses. Thus, our results identify the efferocytosis of eryptotic erythrocytes through AXL/MERTK as a critical mechanism modulating macrophage phenotype and contributing to recovery from ICH. |
ISSN: | 0021-9738 1558-8238 |
DOI: | 10.1172/JCI95612 |
顯示於: | 生理學科所 |
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