The role of the Rap1 GTPase in mediating the inflammatory and anti-microbial functions of macrophages

Large, white blood cells (called macrophages) play a crucial role in protecting the body against harmful viruses, bacteria and other substances, such as pollen, that the immune system recognizes as foreign. These cells trap the foreign substance and signal other cells in the immune system to start the inflammatory process needed to destroy them. Normally, the body tightly regulates the process ensuring that once the invader is destroyed, the inflammatory process is shut down to minimize damage to and promote healing in surrounding tissue. However, sometimes the process goes awry, such that the inflammatory process persists, which can lead to a variety of autoimmune diseases, including hay fever, atherosclerosis, and rheumatoid arthritis. Victor Lei is exploring whether a protein called Rap 1 is involved in activating the immune response to microbial infections by helping white blood cells find infected tissue and initiate inflammation. He is looking in particular to discover whether appropriate Rap1 levels create an effective response to infection, while excessive levels contribute to chronic inflammatory response that could lead to autoimmune diseases. The results of this research could help in the development of drugs that control Rap 1 activity to more effectively combat infections and prevent or minimize the chronic inflammation responsible for arthritis and other conditions.