Mononuclear phagocytes, such as macrophages and microglia, are key regulators of organ homeostasis including vascularization processes. Here, we investigated the role of the suppressor of cytokine signaling 3 (SOCS3) in myeloid cells as a regulator of mononuclear phagocyte function and their interaction with endothelial cells in the context of sprouting angiogenesis. As compared to SOCS3-sufficient counterparts, SOCS3-deficient microglia and macrophages displayed an increased phagocytic activity toward primary apoptotic endothelial cells, which was associated with an enhanced expression of the opsonin growth arrest-specific 6 (Gas6), a major prophagocytic molecule. Furthermore, we found that myeloid SOCS3 deficiency significantly reduced angiogenesis in an ex vivo mouse aortic ring assay, which could be reversed by the inhibition of the Gas6 receptor Mer. Together, SOCS3 in myeloid cells regulates the Gas6/Mer-dependent phagocytosis of endothelial cells, and thereby angiogenesis-related processes. Our findings provide novel insights into the complex crosstalk between mononuclear phagocytes and endothelial cells, and may therefore provide a new platform for the development of new antiangiogenic therapies.

中文翻译：

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髓样 SOCS3 缺陷通过增强的凋亡内皮细胞吞噬调节血管生成。

单核吞噬细胞，如巨噬细胞和小胶质细胞，是器官稳态的关键调节剂，包括血管形成过程。在这里，我们研究了细胞因子信号传导抑制因子 3 (SOCS3) 在骨髓细胞中作为单核吞噬细胞功能的调节剂的作用，以及它们在血管生成的背景下与内皮细胞的相互作用。与 SOCS3 足够的对应物相比，SOCS3 缺陷的小胶质细胞和巨噬细胞对原代凋亡内皮细胞的吞噬活性增加，这与调理素生长停滞特异性 6 (Gas6)（一种主要的促吞噬分子）的表达增强有关。此外，我们发现在体外小鼠主动脉环试验中，骨髓 SOCS3 缺陷显着降低了血管生成，这可以通过抑制 Gas6 受体 Mer 来逆转。总之，骨髓细胞中的 SOCS3 调节内皮细胞的 Gas6/Mer 依赖性吞噬作用，从而调节血管生成相关过程。我们的发现为单核吞噬细胞和内皮细胞之间复杂的串扰提供了新的见解，因此可能为开发新的抗血管生成疗法提供新的平台。