Myeloid Angiogenic Cells Act as Alternative M2 Macrophages and Modulate Angiogenesis through Interleukin-8
Myeloid Angiogenic Cells Act as Alternative M2 Macrophages and Modulate Angiogenesis through Interleukin-8
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DOI：
10.2119/molmed.2011.00129
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发表时间：
2011-09-01
影响因子：
5.7
通讯作者：
Stitt, Alan W.
中科院分区：
文献类型：
--
作者：
Medina, Reinhold J.;O'Neill, Christina L.;Stitt, Alan W.
内皮祖细胞（EPCs）促进血管生成，临床试验表明这种细胞疗法对治疗缺血性疾病是可行的。然而，由于所使用的EPC类型的多样性，临床结果一直是矛盾的。最近，我们的特点是两个EPC亚型，并确定了生长内皮细胞作为唯一的EPC类型与真正的祖细胞和内皮细胞的特点。相比之下，髓样血管生成细胞（MAC）被证明是没有内皮特征的单核细胞，尽管被广泛描述为“EPCs”。“在目前的研究中，我们证明，虽然MAC不会成为内皮细胞或直接纳入微血管网络，但它们可以显着诱导体外内皮管形成和体内血管修复。MAC衍生的白细胞介素-8（IL-8）被确定为一个关键的旁分泌因子，阻断IL-8而不是血管内皮生长因子（VEGF）可阻止MAC诱导的血管生成。细胞外IL-8反式激活VEGF 2并诱导细胞外信号调节激酶的磷酸化。进一步的转录组学和免疫表型分析表明，MAC代表替代活化的M2巨噬细胞。我们的研究结果证明了MAC在血管生成中的明确作用，这与细胞因子如IL-8的旁分泌释放有关。我们还显示，第一次，这些细胞的真实身份作为替代M2巨噬细胞与促血管生成，血管生成和促组织修复性能。(C)2011 Feinstein医学研究所，www.feinsteininstitute.org在线地址：http://www.molmed.org doi：10.2119/molmed.2011.00129
Endothelicl progenitor cells (EPCs) promote angiogenesis, and clinical trials have shown such cell therapy to be feasible for treating ischemic disease. However, clinical outcomes have been contradictory owing to the diverse range of EPC types used. We recently characterized two EPC subtypes, and identified outgrowth endothelial cells as the only EPC type with true progenitor and endothelial characteristics. By contrast, myeloid angiogenic cells (MACs) were shown to be monocytic cells without endothelial characteristics despite being widely described as "EPCs." In the current study we demonstrated that although MACs do not become endothelial cells or directly incorporate into a microvascular network, they can significantly induce endothelial tube formation in vitro and vascular repair in vivo. MAC-derived interleukin-8 (IL-8) was identified as a key paracrine factor, and blockade of IL-8 but not vascular endothelial growth factor (VEGF) prevented MAC-induced angiogenesis. Extracellular IL-8 transactivates VEGFR2 and induces phosphorylation of extracellular signal-regulated kinases. Further transcriptomic and immunophenotypic analysis indicates that MACs represent alternative activated M2 macrophages. Our findings demonstrate an unequivocal role for MACs in angiogenesis, which is linked to paracrine release of cytokines such as IL-8. We also show, for the first time, the true identity of these cells as alternative M2 macrophages with proangiogenic, antiinflammatory and pro-tissue-repair properties. (C) 2011 The Feinstein Institute for Medical Research, www.feinsteininstitute.org Online address: http://www.molmed.org doi: 10.2119/molmed.2011.00129