Hematogenous macrophage depletion reduces the fibrotic scar and increases axonal growth after spinal cord injury.
Hematogenous macrophage depletion reduces the fibrotic scar and increases axonal growth after spinal cord injury.
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DOI：
10.1016/j.nbd.2014.10.024
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发表时间：
2015-02
影响因子：
6.1
通讯作者：
Lee JK
中科院分区：
文献类型：
--
作者：
Zhu Y;Soderblom C;Krishnan V;Ashbaugh J;Bethea JR;Lee JK
脊髓损伤 (SCI) 会导致纤维化疤痕的形成，从而抑制轴突再生。最近的证据表明，纤维化疤痕是由血管周围成纤维细胞形成的，但它们被募集到损伤部位的机制尚不清楚。在脊髓损伤的小鼠模型中使用骨髓移植，我们发现纤维化疤痕中的成纤维细胞与血源性巨噬细胞而不是小胶质细胞相关，后者仅限于周围的星形胶质细胞疤痕。血源性巨噬细胞的消耗导致成纤维细胞密度和基底层形成减少，这与纤维化疤痕中轴突生长的增加有关。巨噬细胞耗竭后的细胞因子基因表达分析表明，Tnfsf8、Tnfsf13（肿瘤坏死因子超家族成员）表达减少和 BMP1-7（骨形态发生蛋白）表达增加可能是抗纤维化机制。我们的研究表明，血源性巨噬细胞是纤维化疤痕形成所必需的，巨噬细胞的消耗会导致多种细胞因子的变化，从而使损伤部位纤维化程度降低，更有利于轴突生长。
Spinal cord injury (SCI) leads to formation of a fibrotic scar that is inhibitory to axon regeneration. Recent evidence indicates that the fibrotic scar is formed by perivascular fibroblasts, but the mechanism by which they are recruited to the injury site is unknown. Using bone marrow transplantation in mouse model of spinal cord injury, we show that fibroblasts in the fibrotic scar are associated with hematogenous macrophages rather than microglia, which are limited to the surrounding astroglial scar. Depletion of hematogenous macrophages results in reduced fibroblast density and basal lamina formation that is associated with increased axonal growth in the fibrotic scar. Cytokine gene expression analysis after macrophage depletion indicates that decreased Tnfsf8, Tnfsf13 (Tumor necrosis factor superfamily members) and increased BMP1-7 (Bone Morphogenetic Proteins) expression may serve as anti-fibrotic mechanisms. Our study demonstrates that hematogenous macrophages are necessary for fibrotic scar formation and macrophage depletion results in changes in multiple cytokines that make the injury site less fibrotic and more conducive to axonal growth.
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影响因子：
16.2
作者：
Burda JE;Sofroniew MV
通讯作者：
Sofroniew MV
影响因子：
32.4
作者：
Fielding, Ceri A.;Jones, Gareth W.;McLoughlin, Rachel M.;McLeod, Louise;Hammond, Victoria J.;Uceda, Javier;Williams, Anwen S.;Lambie, Mark;Foster, Thomas L.;Liao, Chia-Te;Rice, Christopher M.;Greenhill, Claire J.;Colmont, Chantal S.;Hams, Emily;Coles, Barbara;Kift-Morgan, Ann;Newton, Zarabeth;Craig, Katherine J.;Williams, John D.;Williams, Geraint T.;Davies, Simon J.;Humphreys, Ian R.;O'Donnell, Valerie B.;Taylor, Philip R.;Jenkins, Brendan J.;Topley, Nicholas;Jones, Simon A.
通讯作者：
Jones, Simon A.
影响因子：
5.3
作者：
Jung, S;Aliberti, J;Littman, DR
通讯作者：
Littman, DR
影响因子：
2.3
作者：
Jaehrling, Nina;Becker, Klaus;Dodt, Hans-Ulrich
通讯作者：
Dodt, Hans-Ulrich
影响因子：
5.5
作者：
Fenrich, Keith K.;Weber, Pascal;Debarbieux, Franck
通讯作者：
Debarbieux, Franck