Macrophages in homeostasis and cardiovascular disease

巨噬细胞存在于所有主要器官中。这些巨大的吞噬髓系白细胞的主要目的可能是 通过摄取和清除危险或不必要的物质来保持组织的完整性。从清算开始 细菌修剪神经元，巨噬细胞调整自己的功能，以满足其家乡组织的需要。这个 最近认识到组织巨噬细胞来自不同的来源，再加上 环境线索和炎症刺激可以塑造和搅动动态平衡秩序，提供了一个框架 从中我们可以破译巨噬细胞活动的广度和深度。在这里，我将使用：(I) 动脉粥样硬化(LDLR-/-、APOE-/-、PCSK9-Ad)和心肌梗死(永久性结扎、缺血)模型 (2)环境刺激(饮食、睡眠碎片)；(3)转基因和基因敲除小鼠 (Cx3cr1CreERT2 R26-TdT，IL-3-/-，CSF2-/-，Csf2Rb-/-，CD123-/-)；(Iv)外科手术(异种异体，脾 (V)实时成像技术(PET-MRI、活体显微镜)；以及(Vi)许多 免疫学和分子生物学技术研究巨噬细胞的发育和功能 心血管疾病。总的来说，这些工具将允许破译不同器官的巨噬细胞如何 (卵黄囊、胎肝、成人骨髓、成人脾、血管平滑肌细胞)和不同的位置 (外膜、内膜、缺血心肌、远端心肌)相互协作又相互区别 在动脉粥样硬化及其并发症期间。这项赠款的一个中心概念是巨噬细胞之间的张力 作为巨噬细胞功能决定因素的个体发育和组织调节巨噬细胞活动的观点 并取代巨噬细胞个体发育的影响，有利于环境需求。

Macrophages inhabit all major organs. These large phagocytic myeloid leukocytes' primary purpose may be to maintain tissue integrity by ingesting and eliminating dangerous or dispensable material. From clearing bacteria to pruning neurons, macrophages adapt their functions to meet the needs of their home tissues. The recent recognition that tissue macrophages derive from different sources, coupled with the idea that environmental cues and inflammatory stimuli can sculpt and agitate homeostatic order, provides a frame of reference from which we can decipher the breadth and depth of macrophage activity. Here, I will use: (i) models of atherosclerosis (Ldlr–/–, Apoe–/–, PCSK9-Ad) and myocardial infarction (permanent ligation, ischemia reperfusion); (ii) environmental stimuli (diet, sleep fragmentation); (iii) transgenic and knockout mice (Cx3cr1CreERT2 R26-tdT, IL-3–/–, Csf2–/–, Csf2rb–/–, CD123–/–); (iv) surgical procedures (parabiosis, spleen transplantation); (v) real-time imaging technologies (PET-MRI, intravital microscopy); and (vi) many immunology and molecular biology techniques to investigate macrophage development and function in cardiovascular disease. In aggregate, these tools will allow to decipher how macrophages of different orgins (yolk sac, fetal liver, adult bone marrow, adult spleen, vascular smooth muscle cells) and in different locations (adventitia, intima, ischemic myocardium, remote myocardium) collaborate with and differ from one another during atherosclerosis and its complications. A central concept of this grant is the tension between macrophage ontogeny as a determinant of macrophage function and the idea that tissues condition macrophage activities and supplant the influence of macrophage ontogeny in favor of environmental demands.