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

肥大细胞是白细胞，在维持正常器官功能和防止细菌感染方面很重要，但也对哮喘、过敏、肺纤维化（疤痕）和动脉粥样硬化（动脉硬化）等许多疾病的发展起重要作用。它们通过释放许多不同的化学物质来发挥作用：当这些化学物质的释放有限时，效果是有益的，当释放过多时，它们就会变得有害。为了使肥大细胞正常工作，它们与组织中存在的许多细胞类型相互作用，通过粘着它们，这一过程被称为粘附。通过粘附或粘在其他细胞上，这使得肥大细胞能够准确地将它们的化学物质导向特定的细胞类型。我们发现肥大细胞在其表面表达一种有趣的蛋白质，称为细胞粘附分子1 （CADM1）。肥大细胞是不寻常的，因为这种蛋白不被其他白细胞表达。CADM1促进肥大细胞与气道肌细胞和成纤维细胞的相互作用，使细胞粘附在一起，从而进行交流。我们对CADM1的功能知之甚少，也不知道它在气道肌肉和成纤维细胞上结合了什么。因此，在这个项目中，我们希望弄清楚CADM1如何调节肥大细胞的功能，以及它如何与肥大细胞粘附的其他细胞类型相互作用。我们将使用在我们实验室建立的方法来解决这个问题。其中包括一种叫做RNA干扰的专业技术，它可以抑制肥大细胞中产生CADM1的基因。这一研究项目的结果将强调控制CADM1作用的方法，并可能为控制肥大细胞在健康和疾病中的功能提供全新的方法。

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.