The role of cell adhesion molecule-1 in human mast cell biology

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Mast cells are white blood cells which are important in maintaining normal organ function and protection from bacterial infections, but also important for contributing to the development of many diseases such as asthma, allergy, lung fibrosis (scarring) and atherosclerosis (hardening of the arteries). They exert their effects through the release of many diverse chemicals: when release of these is limited the effects are beneficial, when excessive then they become harmful. For mast cells to function normally, they interact with many cell types present in the tissues by sticking to them, a process known as adhesion. By adhering or sticking to other cells, this allows mast cells to direct their chemicals to specific cell types accurately. We have found that mast cells express an interesting protein on their surface called cell adhesion molecule 1 (CADM1). Mast cells are unusual in that this protein is not expressed by other white blood cells. CADM1 facilitates the interaction of mast cells with airway muscle cells and cells called fibroblasts, allowing the cells to stick together and thus communicate. Very little is known about how CADM1 functions, or what it is it binds to on airway muscle and fibroblasts. In this project we therefore wish to work out how CADM1 regulates mast cell function, and how it interacts with other cell types that mast cells stick to. We will use methods that are well established in our laboratory to tackle this. These include a specialist technique called RNA interference which inhibits the gene which produces CADM1 in mast cells. The results of this research project will highlight ways in which the effects of CADM1 can be controlled and may provide entirely new ways of controlling mast cell function in both health and disease.