Macrophages in homeostasis and cardiovascular disease

巨噬细胞存在于所有主要器官中。这些大的吞噬性髓系白细胞的主要目的可能是 通过吸收和消除危险或有害物质来保持组织的完整性。向结算 细菌修剪神经元，巨噬细胞调整其功能，以满足其家庭组织的需要。的 最近认识到，组织巨噬细胞来自不同的来源，再加上这样的想法， 环境线索和炎症刺激可以塑造和破坏稳态秩序，提供了一个框架， 我们可以从中解读巨噬细胞活动的广度和深度。这里，我将使用：用途：（i） 动脉粥样硬化模型（Ldlr-/-、Apoe-/-、PCSK 9-Ad）和心肌梗死模型（永久结扎、缺血 再灌注）;（ii）环境刺激（饮食，睡眠片段）;（iii）转基因和敲除小鼠 （Cx 3cr 1CreERT 2 R26-tdT，IL-3-/-，Csf 2-/-，Csf 2 rb-/-，CD 123-/-）;（iv）外科手术（联体共生，脾 （v）实时成像技术（PET-MRI，活体显微镜检查）;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来源的巨噬细胞 (yolk囊、胎肝、成人骨髓、成人脾、血管平滑肌细胞）和不同位置 （外膜、内膜、缺血心肌、远端心肌）相互协作，相互不同 动脉粥样硬化及其并发症。这项资助的一个中心概念是巨噬细胞之间的紧张关系， 个体发育作为巨噬细胞功能的决定因素，以及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，以满足环境需求。

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.