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Local oxidised phospholipids within the pleural cavity: fuelling macrophage response during inflammation?

胸膜腔内局部氧化磷脂：炎症期间促进巨噬细胞反应？

基本信息

批准号：
MR/V031767/1
负责人：
Lucy Helen Jackson-Jones
金额：
$ 76.89万
依托单位：
Lancaster University
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2021
资助国家：
英国
起止时间：
2021 至无数据
项目状态：
未结题

来源：
https://gtr.ukri.org/projects?ref=MR%2FV031767%2F1
关键词：
Local oxidised phospholipids within pleural

项目摘要

Inflammation as part of the immune response is the body's normal reaction to injury & infection. Inflammation is related to many life threatening conditions & is particularly associated with respiratory problems. In our chests, the pleural space that exists between the ribcage & lungs is lined by specialised cells that secrete small amounts of pleural fluid. Pleural fluid contains immune cells, in particular large numbers of cells known as macrophages or 'big-eaters'. Pleural macrophages provide a significant layer of protection against external pathogens, allergens & carcinogens that enter the body via the lungs. Cholesterol is an essential fat required during normal physiology, too much cholesterol can be toxic and so production, storage & movement of cholesterol around the body is tightly regulated. Lipo-proteins are mixtures of fats & cholesterol packaged up for delivery around the body. Macrophages can use fats as a fuel source and are able to obtain them via uptake of lipo-proteins present within bodily fluids. Antibodies are proteins that can recognise & bind infectious & damage associated molecules often resulting in their clearance from the body. We have identified that during inflammation related to an allergic-like response in the pleural space there are increased levels of antibodies that recognise lipo-proteins and the macrophages at the site of inflammation begin to make their own cholesterol. In this project we want to determine whether lipo-proteins are produced locally within the pleural space in the absence, as well as in the presence, of different types of lung inflammation. We will aim to determine what induces their production and if recognition & uptake of these lipid species controls the normal function of pleural macrophages. Are macrophages 'eating' these lipids in order to make energy? Do the lipids damage the cells? Are the lipids required for macrophages to divide? Do antibodies modify the ability of macrophages to detect these lipids? Does blockade of macrophage lipid detection turn on cellular cholesterol synthesis? What is the cholesterol used for?Solutions to these questions will lead to profound changes in our understanding of the inflammatory processes associated with respiratory disease as well as offering new targets for both therapeutic intervention and diagnostics.

炎症作为免疫反应的一部分是身体对损伤和感染的正常反应。炎症与许多危及生命的疾病有关，特别是与呼吸问题有关。在我们的胸腔中，胸腔与肺之间的胸膜空间由分泌少量胸膜液的专门细胞排列。胸腔液含有免疫细胞，特别是大量的细胞称为巨噬细胞或“大食者”。胸膜巨噬细胞提供了一个重要的保护层，防止通过肺部进入体内的外部病原体，过敏原和致癌物质。胆固醇是正常生理过程中所需的必需脂肪，过多的胆固醇可能是有毒的，因此胆固醇在身体周围的生产，储存和运动受到严格控制。脂蛋白是脂肪和胆固醇的混合物，被包装在身体周围。巨噬细胞可以使用脂肪作为燃料来源，并能够通过摄取体液中存在的脂蛋白来获得它们。抗体是可以识别和结合感染和损伤相关分子的蛋白质，通常导致其从体内清除。我们已经确定，在胸膜腔中与过敏样反应相关的炎症期间，识别脂蛋白的抗体水平增加，并且炎症部位的巨噬细胞开始产生它们自己的胆固醇。在这个项目中，我们想确定是否脂蛋白在胸膜腔内产生的情况下，以及在存在不同类型的肺部炎症。我们的目标是确定是什么诱导了它们的产生，以及这些脂质种类的识别和摄取是否控制了胸膜巨噬细胞的正常功能。巨噬细胞“吃”这些脂质是为了制造能量吗？脂质会损害细胞吗？脂质是巨噬细胞分裂所必需的吗？抗体是否改变了巨噬细胞检测这些脂质的能力？巨噬细胞脂质检测的阻断是否开启细胞胆固醇合成？胆固醇有什么用？这些问题的解决方案将导致我们对呼吸系统疾病相关炎症过程的理解发生深刻变化，并为治疗干预和诊断提供新的靶点。