Characterisation of a novel Fc conjugate of macrophage colony-stimulating factor.
Characterisation of a novel Fc conjugate of macrophage colony-stimulating factor.
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DOI：
10.1038/mt.2014.112
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发表时间：
2014-09
期刊：
影响因子：
--
通讯作者：
Hume DA
中科院分区：
文献类型：
--
作者：
Gow DJ;Sauter KA;Pridans C;Moffat L;Sehgal A;Stutchfield BM;Raza S;Beard PM;Tsai YT;Bainbridge G;Boner PL;Fici G;Garcia-Tapia D;Martin RA;Oliphant T;Shelly JA;Tiwari R;Wilson TL;Smith LB;Mabbott NA;Hume DA
我们已经产生了具有改善的循环半衰期的集落刺激因子（CSF）1的Fc缀合物。CSF 1-Fc保留其巨噬细胞生长促进活性，并且在体外不诱导促炎细胞因子。用CSF 1-Fc处理在小鼠或猪中未产生不良作用。在Mac绿色小鼠中使用Csf 1 r增强的绿色荧光蛋白（EGFP）报告基因检查CSF 1-Fc的影响。向小鼠施用CSF 1-Fc驱动Csf 1 r-EGFP阳性巨噬细胞广泛浸润所有组织。主要后果是肝脾肿大，与肝细胞增殖相关。肝脏的表达谱表明，浸润的巨噬细胞产生肝细胞增殖的候选介质，包括尿激酶，肿瘤坏死因子和白细胞介素6。CSF 1-Fc还促进破骨细胞生成，并对其他器官系统产生多效性作用，特别是睾丸，其中CSF 1依赖性巨噬细胞参与稳态。然而，它不影响其他推定的CSF 1靶点，特别是肠道，其中潘氏细胞数量和绒毛结构没有变化。CSF 1在多器官再生医学中具有治疗潜力。我们认为CSF 1-Fc偶联物保留了这种潜力，并且可以允许通过注射而不是核心分子所需的连续输注进行每日递送。
We have produced an Fc conjugate of colony-stimulating factor (CSF) 1 with an improved circulating half-life. CSF1-Fc retained its macrophage growth-promoting activity, and did not induce proinflammatory cytokines in vitro. Treatment with CSF1-Fc did not produce adverse effects in mice or pigs. The impact of CSF1-Fc was examined using the Csf1r-enhanced green fluorescent protein (EGFP) reporter gene in MacGreen mice. Administration of CSF1-Fc to mice drove extensive infiltration of all tissues by Csf1r-EGFP positive macrophages. The main consequence was hepatosplenomegaly, associated with proliferation of hepatocytes. Expression profiles of the liver indicated that infiltrating macrophages produced candidate mediators of hepatocyte proliferation including urokinase, tumor necrosis factor, and interleukin 6. CSF1-Fc also promoted osteoclastogenesis and produced pleiotropic effects on other organ systems, notably the testis, where CSF1-dependent macrophages have been implicated in homeostasis. However, it did not affect other putative CSF1 targets, notably intestine, where Paneth cell numbers and villus architecture were unchanged. CSF1 has therapeutic potential in regenerative medicine in multiple organs. We suggest that the CSF1-Fc conjugate retains this potential, and may permit daily delivery by injection rather than continuous infusion required for the core molecule.
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影响因子：
--
作者：
AKERMAN, P;COTE, P;DIEHL, AM
通讯作者：
DIEHL, AM
影响因子：
6.2
作者：
Alexander, Kylie A.;Chang, Ming K.;Pettit, Allison R.
通讯作者：
Pettit, Allison R.
影响因子：
14.5
作者：
Boissonneault, Vincent;Filali, Mohammed;Rivest, Serge
通讯作者：
Rivest, Serge
DOI：
10.1084/jem.20120412
发表时间：
2013-01-14
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Luo J;Elwood F;Britschgi M;Villeda S;Zhang H;Ding Z;Zhu L;Alabsi H;Getachew R;Narasimhan R;Wabl R;Fainberg N;James ML;Wong G;Relton J;Gambhir SS;Pollard JW;Wyss-Coray T
通讯作者：
Wyss-Coray T
影响因子：
4.4
作者：
Hume, David A.;Summers, Kim M.;Freeman, Thomas C.
通讯作者：
Freeman, Thomas C.