Macrophage sensing of extracellular ATP during inflammation

炎症是身体对感染和损伤等威胁的反应。在炎症过程中，身体会释放危险信号，提醒免疫细胞有什么不对劲。第一个遇到这些信号的免疫细胞被称为巨噬细胞，它们的主要工作是摧毁威胁，并呼吁备份，以完全对抗危险，以恢复健康。然而，有时免疫系统失败，即使威胁消失，炎症仍在继续。在这些情况下，曾经是你最好的朋友可能很快成为你最大的敌人。没有什么可以摧毁巨噬细胞现在会攻击你自己的身体并造成损害。这是许多炎症性疾病的原因，包括关节炎，心血管疾病或肺部疾病，如COPD（慢性阻塞性肺疾病）。在感知到危险时，巨噬细胞的行为就像工厂装配厂，把很多零件放在一起，以便制造正确的大炮来战斗和消除威胁。这些不同的片段被称为蛋白质，它们需要在正确的位置以特定的顺序组装才能正常工作。如果这些蛋白质的组装发生在错误的时间或错误的顺序，它可能会引起慢性炎症，从而导致疾病。巨噬细胞可以感知的危险信号之一是ATP。ATP只存在于健康的细胞中，但当细胞受到压力时，它们会将其释放到周围环境中。巨噬细胞通过一种名为P2X7R的蛋白质感知ATP，启动一系列导致炎症的事件（或装配线）。然而，我们不知道这些事件是什么，以及它们是如何被管理的。在这里，我们将研究当ATP被巨噬细胞感知时，不同的装配线是如何启动的。我们将研究哪些蛋白质是必需的，以何种顺序，以及这些蛋白质在COPD等炎症性疾病中是否有缺陷。了解这一点将对炎症性疾病患者产生有益的影响，因为这将有助于开发可以逆转或阻止炎症以实现健康的新药。

Inflammation is the response of the body to threats such as infection and injury. During inflammation, the body releases danger signals that alert immune cells that something is wrong. The first immune cells to encounter these signals are called macrophages and their main job is to destroy the threat and call for back up to completely fight the danger to restore health. However sometimes the immune system fails and inflammation continues even when the threat is gone. In these cases what was once your best friend can quickly become your worst enemy. With nothing to destroy macrophages will now attack your own body and cause damage. This is the cause of many inflammatory conditions including arthritis, cardiovascular disease or lung diseases such as COPD (Chronic Obstructive Pulmonary Disorders).Upon sensing danger macrophages behave like factory assembly plants, putting a lot of pieces together in order to manufacture the right artillery to fight and remove the threat. These different pieces are called proteins and they need to be assembled in the right place and in a specific order to function properly. If the assembly of these proteins occurs in the wrong moment or in the wrong order it can misfire causing chronic inflammation, and consequently disease. One of the danger signals that macrophages can sense is ATP. ATP is only found within healthy cells, but when cells become stressed they release it into their surrounding environment. Macrophages sense ATP through a protein called P2X7R initiating a series of events (or assembly lines) that lead to inflammation. However we do not understand what these events are and how they are regulated. Here we will investigate how the different assembly lines initiated when ATP is sensed by macrophages work. We will investigate which proteins are required, in which order and if these are faulty in inflammatory conditions such as COPD. Understanding this would have a beneficial effect in people with inflammatory disease since this will help to develop new drugs that could reverse or stop inflammation to achieve health.