Macrophage sensing of extracellular ATP during inflammation

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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.