In vivo investigation of non-classical monocyte patrolling mechanism

非经典单核细胞巡逻机制的体内研究

基本信息

批准号：
9124682
负责人：
Paola Marcovecchio
金额：
$ 3.62万
依托单位：
LA JOLLA INSTITUTE FOR IMMUNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-05-01 至 2019-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9124682
关键词：
Adaptor Signaling Protein Adherence Affect Affinity Atherosclerosis Behavior Binding Biological Assay Blood Blood Circulation Blood Platelets Blood Vessels Blood flow CCR5 gene CD36 gene Cardiovascular Diseases Cardiovascular system Carotid Artery Ulcerating Plaque Cell surface Cells Cessation of life Characteristics Cholesterol Chronic Data Disease Endothelial Cells Endothelium Exposure to Fatty acid glycerol esters Foam Cells Frequencies Future Heart Diseases High Fat Diet Human Immune In Vitro Inflammation Inflammation Mediators Inflammatory Integrin alpha Chains Integrin beta Chains Integrins Investigation Knock-out Leukocyte Trafficking Ligands Literature Low-Density Lipoproteins Mediating Modeling Molecular Conformation Mus Necrosis Pathway interactions Play Process Resolution Role SR-B proteins Selectins Signal Transduction Site Surveys Testing Time Vascular Cell Adhesion Molecule-1 Work atherogenesis atheroprotective cell type chemokine cytokine feeding in vivo macrophage monocyte novel oxidized lipid oxidized low density lipoprotein prevent public health relevance receptor binding receptor function scavenger receptor therapeutic target uptake vascular inflammation western diet

Adaptor Signaling Protein Adherence Affect Affinity Atherosclerosis Behavior Binding Biological Assay Blood Blood Circulation Blood Platelets Blood Vessels Blood flow CCR5 gene CD36 gene Cardiovascular Diseases Cardiovascular system Carotid Artery Ulcerating Plaque Cell surface Cells Cessation of life Characteristics Cholesterol Chronic Data Disease Endothelial Cells Endothelium Exposure to Fatty acid glycerol esters Foam Cells Frequencies Future Heart Diseases High Fat Diet Human Immune In Vitro Inflammation Inflammation Mediators Inflammatory Integrin alpha Chains Integrin beta Chains Integrins Investigation Knock-out Leukocyte Trafficking Ligands Literature Low-Density Lipoproteins Mediating Modeling Molecular Conformation Mus Necrosis Pathway interactions Play Process Resolution Role SR-B proteins Selectins Signal Transduction Site Surveys Testing Time Vascular Cell Adhesion Molecule-1 Work atherogenesis atheroprotective cell type chemokine cytokine feeding in vivo macrophage monocyte novel oxidized lipid oxidized low density lipoprotein prevent public health relevance receptor binding receptor function scavenger receptor therapeutic target uptake vascular inflammation western diet

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项目摘要

DESCRIPTION (provided by applicant): Blood monocytes circulate in the periphery as predominantly two subsets: classical and non- classical, or patrolling, monocytes. It has been shown that classical monocytes contribute early on to the process of atherosclerosis by adhering to the vasculature and migrating to the inner layers of the vessel wall, primarily using selectins and integrins, to eventually become foam cells, leading to a chronic inflammatory state within the vascular layers. The endothelial layer of the blood vessel also becomes activated, releasing pro-inflammatory cytokines and chemokines as well as upregulating integrin ligands such as VCAM-1. Non-classical monocytes have been shown to migrate to plaque sites, although they are less frequent than classical monocytes inside the plaque and upregulate different cell surface markers. During steady state, these non-classical monocytes will spend prolonged times crawling non-directionally along the endothelium to survey the vasculature, although more frequently found in smaller vessels than larger vessels. We have found that during atherogenesis, by feeding mice a western diet that is high in fat and cholesterol, there is a significant increase in the patrolling activity of non-classical monocytes. Previous work in our lab has suggested that these monocytes are atheroprotective, as their absence leads to increases in plaque size and inflammatory monocyte numbers. The function of these non-classical monocytes in atherosclerosis, and the exact mechanism of patrolling, is still unclear, but by studying how non-classical monocytes are activated by this disease, we may be able to elucidate a novel target for treating vascular inflammation and plaque formation.

描述（由适用提供）：周围的血单核细胞圆，主要是两个子集：经典和非古典或巡逻单核细胞。已经表明，经典的单核细胞通过粘附在血管系统上并迁移到血管壁的内层（主要使用Selectins和整合素）来最终成为泡沫细胞，从而导致血管内的慢性炎症状态。血管的内皮层也被激活，释放出促炎性细胞因子和趋化因子以及上调整联蛋白配体（如VCAM-1）。非古典单核细胞已显示出迁移到牙菌斑位点，尽管它们的频率低于斑块内的经典单核细胞并上调不同的细胞表面标记。在稳态期间，这些非古典单核细胞将花费长时间的时间沿着原始疗法进行非方向爬行以调查脉管系统，尽管在较小的血管中比较大的容器更频繁地发现。我们发现，在动脉粥样硬化期间，通过给小鼠喂养脂肪和胆固醇高的西方饮食，非经典单核细胞的巡逻活性显着增加。我们实验室中的先前工作表明，这些单核细胞是动脉保护性的，因为它们的缺失导致牙菌斑的增加，这些非经典单核细胞在动脉粥样硬化中的功能以及巡逻的确切机制仍然不清楚，但是通过研究这种疾病的非古典单细胞的表现，我们可以将其置入素养的形式，从而使绿色素养的效果能够置换，从而使vaste caption cante canter and Inflection anction Inflection and Inflection and Inflection Indection caltion Indection and cante and Indection coptiation。