Primitive Embryonic Macrophages are Required for Coronary Development and Maturation.
Primitive Embryonic Macrophages are Required for Coronary Development and Maturation.
复制标题
冠状动脉发育和成熟需要原始的胚胎巨噬细胞。
DOI：
10.1161/circresaha.115.308270
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发表时间：
2016-05-13
影响因子：
20.1
通讯作者：
Lavine KJ
中科院分区：
文献类型：
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作者：
Leid J;Carrelha J;Boukarabila H;Epelman S;Jacobsen SE;Lavine KJ
现在已经认识到，存在于发育和成人组织中的巨噬细胞来自不同的祖细胞，包括胚胎起源的祖细胞。尽管巨噬细胞在成年生物中的功能已经得到了很好的研究，但巨噬细胞在器官发育中的功能在很大程度上仍然不明确。此外，不同的巨噬细胞谱系是否具有不同的功能尚不清楚。为了解决这些问题，我们研究了发育中的心脏中巨噬细胞亚群的功能，这是一个充满胚胎源性巨噬细胞的器官。利用流式细胞术、免疫染色和遗传谱系追踪的结合，我们证明发育中的心脏包含一系列复杂的胚胎巨噬细胞亚群，可分为源自原始卵黄囊的趋化因子（C-C基序）受体2 -和趋化因子（C-C基序）受体2+巨噬细胞、重组激活基因1+淋巴细胞和fms样酪氨酸激酶3+胎儿单核细胞谱系。功能上，卵黄囊来源的趋化因子（C-C基序）受体2 -巨噬细胞在冠状动脉发育中起重要作用，它们是原始冠状动脉丛重塑所必需的。在机制上，趋化因子（C-C基序）受体2 -巨噬细胞在冠状动脉灌注开始时被招募到冠状血管，通过选择性扩张灌注血管介导冠状动脉丛重塑。我们进一步证明胰岛素样生长因子信号可能介导胚胎源性巨噬细胞的促血管生成特性。总之，这些发现表明胚胎心脏包含具有独特功能的胚胎巨噬细胞的不同谱系，并揭示了控制冠状动脉发育的新机制。
It is now recognized that macrophages residing within developing and adult tissues are derived from diverse progenitors including those of embryonic origin. Although the functions of macrophages in adult organisms are well studied, the functions of macrophages during organ development remain largely undefined. Moreover, it is unclear whether distinct macrophage lineages have differing functions. To address these issues, we investigated the functions of macrophage subsets resident within the developing heart, an organ replete with embryonic-derived macrophages. Using a combination of flow cytometry, immunostaining, and genetic lineage tracing, we demonstrate that the developing heart contains a complex array of embryonic macrophage subsets that can be divided into chemokine (C-C motif) receptor 2− and chemokine (C-C motif) receptor 2+ macrophages derived from primitive yolk sac, recombination activating gene 1+ lymphomyeloid, and Fms-like tyrosine kinase 3+ fetal monocyte lineages. Functionally, yolk sac–derived chemokine (C-C motif) receptor 2− macrophages are instrumental in coronary development where they are required for remodeling of the primitive coronary plexus. Mechanistically, chemokine (C-C motif) receptor 2− macrophages are recruited to coronary blood vessels at the onset of coronary perfusion where they mediate coronary plexus remodeling through selective expansion of perfused vasculature. We further demonstrate that insulin like growth factor signaling may mediate the proangiogenic properties of embryonic-derived macrophages. Together, these findings demonstrate that the embryonic heart contains distinct lineages of embryonic macrophages with unique functions and reveal a novel mechanism that governs coronary development.