Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Department of Cell and Development Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Nat Cardiovasc Res. 2022 Jan;1(1):67-84. doi: 10.1038/s44161-021-00006-4. Epub 2022 Jan 12.
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 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.
白细胞和内皮细胞经常合作以解决炎症事件。在大多数情况下，这些相互作用是短暂的，是由免疫损伤引发的。在这里，我们报告称，在血流紊乱的区域，主动脉内皮细胞会与一群特殊的巨噬细胞永久而紧密地结合，这些巨噬细胞在出生时从正在关闭的动脉导管招募而来，与内皮细胞共享管腔表面，并在内膜中交织在一起。影响血液动力学的解剖学变化，如动脉导管未闭，会改变巨噬细胞的定植，使其与血流紊乱的区域一致。主动脉驻留巨噬细胞通过直接细胞更新而扩张。诱导性耗尽内膜巨噬细胞会导致凝血酶介导的内皮细胞收缩、纤维蛋白逐渐积累，并形成微血栓，一旦脱落，就会导致多个器官的血管阻塞。这些发现表明，血管内驻留巨噬细胞对于调节血流紊乱区域的凝血酶活性和清除纤维蛋白沉积至关重要。
