Macrophages in homeostasis and cardiovascular disease

巨噬细胞在体内平衡和心血管疾病中的作用

• 批准号: 9883830
• 负责人: Filip K Swirski
• 金额: $ 84.39万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-03-01 至 2024-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9883830
• 关键词: Adult; Apolipoprotein E; Atherosclerosis; Bacteria; Bone Marrow; Cardiovascular Diseases; Cells; Coupled; Cues; Dangerousness; Development; Diet; Environment; Fetal Liver; Grant; Growth; Home environment; Homeostasis; IL3 Gene; IL3RA gene; Imaging technology; Immunology; Inflammatory; Ingestion; Ischemia; Knockout Mice; Leukocytes; Ligation; Location; Magnetic Resonance Imaging; Modeling; Molecular Biology Techniques; Myelogenous; Myocardial Infarction; Myocardial Ischemia; Myocardium; Nature; Neurons; Operative Surgical Procedures; Organ; Parabiosis; Phagocytes; Positron-Emission Tomography; Reperfusion Therapy; Shapes; Sleep Fragmentations; Smooth Muscle Myocytes; Source; Spleen; Stimulus; Tissues; Transgenic Mice; Tunica Adventitia; Vascular Smooth Muscle; Yolk Sac; intravital microscopy; macrophage; real-time images; scaffold; spleen transplantation; tool

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.