On-site education of VEGF-recruited monocytes improves their performance as angiogenic and arteriogenic accessory cells.
On-site education of VEGF-recruited monocytes improves their performance as angiogenic and arteriogenic accessory cells.
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DOI：
10.1084/jem.20120690
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发表时间：
2013-11-18
期刊：
影响因子：
--
通讯作者：
Keshet E
中科院分区：
文献类型：
--
作者：
Avraham-Davidi I;Yona S;Grunewald M;Landsman L;Cochain C;Silvestre JS;Mizrahi H;Faroja M;Strauss-Ayali D;Mack M;Jung S;Keshet E
vegf驱动的新生血管短暂募集ly6high单核细胞，随后改变其表型并发挥血管生成功能以扩大小血管。成人新生血管的形成依赖于单核细胞向靶器官或肿瘤的募集，并在其中作为旁分泌辅助细胞发挥作用。募集单核细胞的确切起源及其可塑性的机制尚不清楚。使用基于vegf的转基因系统，其中基因标记的单核细胞被有条件地召唤到肝脏，作为vegf启动的血管生成程序的一部分，我们表明这些募集的细胞来源于丰富的循环Ly6Chi单核细胞池。然而，值得注意的是，单核细胞到达vegf诱导的器官而不是原始器官后，会经历多种表型和功能变化，赋予它们增强的促血管生成能力，更重要的是，具有显著增加的将现有小血管改造成更大导管的能力。值得注意的是，单核细胞不会分化为长寿命的巨噬细胞，而是作为短暂的附属细胞出现。预先设定的亚群转移和一种新的串联转移策略的结果排除了对专门的预先存在的亚群的选择性招募或现场选择，从而加强了主动重编程作为提高性能的潜在机制。总的来说，这项研究揭示了VEGF的一个新功能，即在现场培养招募的“标准”单核细胞成为血管生成和动脉生成的专业细胞，这一发现也可能有助于更好地设计血管生成疗法。
VEGF-driven neovascularization transiently recruits Ly6Chigh monocytes, which subsequently alter their phenotype and exert angiogenic function to enlarge small vessels. Adult neovascularization relies on the recruitment of monocytes to the target organ or tumor and functioning therein as a paracrine accessory. The exact origins of the recruited monocytes and the mechanisms underlying their plasticity remain unclear. Using a VEGF-based transgenic system in which genetically tagged monocytes are conditionally summoned to the liver as part of a VEGF-initiated angiogenic program, we show that these recruited cells are derived from the abundant pool of circulating Ly6Chi monocytes. Remarkably, however, upon arrival at the VEGF-induced organ, but not the naive organ, monocytes undergo multiple phenotypic and functional changes, endowing them with enhanced proangiogenic capabilities and, importantly, with a markedly increased capacity to remodel existing small vessels into larger conduits. Notably, monocytes do not differentiate into long-lived macrophages, but rather appear as transient accessory cells. Results from transfers of presorted subpopulations and a novel tandem transfer strategy ruled out selective recruitment of a dedicated preexisting subpopulation or onsite selection, thereby reinforcing active reprogramming as the underlying mechanism for improved performance. Collectively, this study uncovered a novel function of VEGF, namely, on-site education of recruited “standard” monocytes to become angiogenic and arteriogenic professional cells, a finding that may also lend itself for a better design of angiogenic therapies.
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影响因子：
37.8
作者：
Khurana, R;Moons, L;Zachary, IC
通讯作者：
Zachary, IC
影响因子：
5.3
作者：
Jung, S;Aliberti, J;Littman, DR
通讯作者：
Littman, DR
影响因子：
20.1
作者：
Pipp, F;Heil, M;Clauss, M
通讯作者：
Clauss, M
DOI：
10.1084/jem.20070885
发表时间：
2007-11-26
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Nahrendorf M;Swirski FK;Aikawa E;Stangenberg L;Wurdinger T;Figueiredo JL;Libby P;Weissleder R;Pittet MJ
通讯作者：
Pittet MJ
影响因子：
11.4
作者：
Dor, Y;Djonov, V;Keshet, E
通讯作者：
Keshet, E