Aortic intimal resident macrophages are essential for maintenance of the non-thrombogenic intravascular state.
Aortic intimal resident macrophages are essential for maintenance of the non-thrombogenic intravascular state.
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DOI：
10.1038/s44161-021-00006-4
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发表时间：
2022-01
期刊：
影响因子：
--
通讯作者：
Iruela-Arispe, M Luisa
中科院分区：
文献类型：
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作者：
Hernandez, Gloria E;Ma, Feiyang;Martinez, Guadalupe;Firozabadi, Nadia B;Salvador, Jocelynda;Juang, Lih Jiin;Leung, Jerry;Zhao, Peng;Lopez, Diego A;Ardehali, Reza;Beaudin, Anna E;Kastrup, Christian J;Pellegrini, Matteo;Flick, Matthew J;Iruela-Arispe, M Luisa
白细胞和内皮细胞经常合作解决炎症事件。在大多数情况下，这些相互作用本质上是短暂的，并由免疫侮辱触发。在这里，我们报道在血流紊乱的区域，主动脉内皮细胞与一群特殊的巨噬细胞永久和密切地联系在一起，这些巨噬细胞是在出生时从闭合的动脉导管招募的，与内皮细胞共享管腔表面，并与内膜交织在一起。影响血流动力学的解剖学变化，如动脉导管未闭，会改变巨噬细胞的种植，使其与血流紊乱的区域重合。主动脉驻留巨噬细胞通过直接细胞更新在原位扩张。内膜巨噬细胞的诱导耗竭导致凝血酶介导的内皮细胞收缩，纤维蛋白的进行性聚集和微血栓的形成，一旦被清除，就会导致几个器官的血管阻塞。总而言之，这些发现表明，血管内驻留的巨噬细胞对于调节凝血酶活性和清除血流紊乱区域的纤维蛋白沉积至关重要。
Leukocytes and endothelial cells frequently cooperate to resolve inflammatory events. In most cases, these interactions are transient in nature and triggered by immunological insults. Here, we report that in areas of disturbed blood flow, aortic endothelial cells permanently and intimately associate with a population of specialized macrophages that are recruited at birth from the closing ductus arteriosus and share the luminal surface with the endothelium becoming interwoven in the tunica intima. Anatomical changes that affect hemodynamics, like in patent ductus arteriosus, alter macrophage seeding to coincide with regions of disturbed flow. Aortic resident macrophages expand in situ via direct cell renewal. Induced-depletion of intimal macrophages led to thrombin-mediated endothelial cell contraction, progressive fibrin accumulation and formation of microthrombi that, once dislodged, caused blockade of vessels in several organs. Together the findings revealed that intravascular resident macrophages are essential to regulate thrombin activity and clear fibrin deposits in regions of disturbed blood flow.