Characteristics of the alternative phenotype of microglia/macrophages and its modulation in experimental gliomas.
Characteristics of the alternative phenotype of microglia/macrophages and its modulation in experimental gliomas.
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DOI：
10.1371/journal.pone.0023902
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Kaminska B
中科院分区：
文献类型：
--
作者：
Gabrusiewicz K;Ellert-Miklaszewska A;Lipko M;Sielska M;Frankowska M;Kaminska B
小胶质细胞（脑内巨噬细胞）在恶性胶质瘤中积累，它们不是启动抗肿瘤反应，而是通过释放细胞因子/趋化因子和细胞外基质蛋白酶转变为促侵袭表型，支持肿瘤生长、侵袭、血管生成和免疫抑制。使用免疫荧光和流式细胞术，我们证明了早期积累的激活小胶质细胞，然后在实验小鼠EGFP-GL 261胶质瘤巨噬细胞的积累。这些细胞获得替代表型，如通过评价来自肿瘤组织的磁性分选的CD 11b+细胞中的10种促炎/抗炎细胞因子的产生和28种基因的表达谱所证明的。此外，我们发现，植入胶质瘤的变形虫，Iba 1阳性细胞的浸润可以减少系统注射环孢素A（CsA）细胞接种后两天或八天。CsA处理的小鼠中，IL-10和GM-CSF的上调水平，胶质瘤衍生的CD 11b+细胞中替代和促侵袭表型的特征性基因（arg-1，mt 1-mmp，cxcl 14）的表达增加，以及血管生成和肿瘤生长的增强均降低。我们的研究结果首次定义了神经胶质瘤浸润性小胶质细胞/巨噬细胞的动力学和生化特征。抑制肿瘤浸润性巨噬细胞的交替活化显著降低了肿瘤生长。因此，阻断小胶质细胞/巨噬细胞浸润及其促侵袭功能可能是恶性胶质瘤的一种新的治疗策略。
Microglia (brain resident macrophages) accumulate in malignant gliomas and instead of initiating the anti-tumor response, they switch to a pro-invasive phenotype, support tumor growth, invasion, angiogenesis and immunosuppression by release of cytokines/chemokines and extracellular matrix proteases. Using immunofluorescence and flow cytometry, we demonstrate an early accumulation of activated microglia followed by accumulation of macrophages in experimental murine EGFP-GL261 gliomas. Those cells acquire the alternative phenotype, as evidenced by evaluation of the production of ten pro/anti-inflammatory cytokines and expression profiling of 28 genes in magnetically-sorted CD11b+ cells from tumor tissues. Furthermore, we show that infiltration of implanted gliomas by amoeboid, Iba1-positive cells can be reduced by a systematically injected cyclosporine A (CsA) two or eight days after cell inoculation. The up-regulated levels of IL-10 and GM-CSF, increased expression of genes characteristic for the alternative and pro-invasive phenotype (arg-1, mt1-mmp, cxcl14) in glioma-derived CD11b+ cells as well as enhanced angiogenesis and tumor growth were reduced in CsA-treated mice. Our findings define for the first time kinetics and biochemical characteristics of glioma-infiltrating microglia/macrophages. Inhibition of the alternative activation of tumor-infiltrating macrophages significantly reduced tumor growth. Thus, blockade of microglia/macrophage infiltration and their pro-invasive functions could be a novel therapeutic strategy in malignant gliomas.
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影响因子：
15.9
作者：
Hussain, S. Farzana;Yang, David;Heimberger, Amy B.
通讯作者：
Heimberger, Amy B.
影响因子：
6.1
作者：
Narumiya, S
通讯作者：
Narumiya, S
DOI：
10.4049/jimmunol.0902009
发表时间：
2010-06-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Herbert DR;Orekov T;Roloson A;Ilies M;Perkins C;O'Brien W;Cederbaum S;Christianson DW;Zimmermann N;Rothenberg ME;Finkelman FD
通讯作者：
Finkelman FD
影响因子：
3.3
作者：
Cha, S;Johnson, G;Turnbull, DH
通讯作者：
Turnbull, DH
DOI：
10.1016/0885-4505(86)90070-8
发表时间：
1986-04-01
期刊：
BIOCHEMICAL MEDICINE AND METABOLIC BIOLOGY
影响因子：
--
作者：
KONARSKA, L;TOMASZEWSKI, L
通讯作者：
TOMASZEWSKI, L