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

炎症作为免疫反应的一部分，是人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，尤其与呼吸问题有关。在我们的胸腔中，胸腔和肺之间的胸膜空间由分泌少量胸液的特殊细胞排列。胸腔积液中含有免疫细胞，尤其是大量的巨噬细胞或食量大的细胞。胸膜巨噬细胞提供了一层重要的保护层，以抵御外部病原体、过敏原和通过肺部进入人体的致癌物。胆固醇是正常生理所需的一种基本脂肪，过多的胆固醇可能是有毒的，因此胆固醇在人体内的产生、储存和移动受到严格的调控。脂肪蛋白是脂肪和胆固醇的混合物，被包装起来运往全身。巨噬细胞可以利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脂肪。抗体是一种蛋白质，可以识别和结合与感染和损伤相关的分子，通常会导致它们从体内清除。我们已经发现，在与胸膜腔过敏样反应相关的炎症过程中，识别脂蛋白的抗体水平增加，炎症部位的巨噬细胞开始制造自己的胆固醇。在这个项目中，我们想要确定在没有不同类型的肺部炎症的情况下，以及在存在不同类型的肺部炎症的情况下，是否在胸膜腔局部产生脂蛋白。我们的目标是确定是什么诱导了它们的产生，以及对这些脂质物种的识别和摄取是否控制了胸膜巨噬细胞的正常功能。巨噬细胞是不是为了制造能量而“吞噬”这些脂类？这些脂类会损害细胞吗？巨噬细胞分裂所需的脂类吗？抗体是否会改变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会影响细胞胆固醇的合成？胆固醇的用途是什么？这些问题的解决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。

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.