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

肥大细胞是白色血细胞，其在维持正常器官功能和保护免受细菌感染方面是重要的，但对于促进许多疾病如哮喘、过敏、肺纤维化（瘢痕形成）和动脉粥样硬化（动脉硬化）的发展也是重要的。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受到限制时，效果是有益的，当过度时，它们就会变得有害。为了使肥大细胞正常发挥功能，它们通过粘附与组织中存在的许多细胞类型相互作用，这一过程称为粘附。通过粘附或粘附到其他细胞上，这使得肥大细胞能够准确地将其化学物质引导到特定的细胞类型。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，因为这种蛋白质不被其他白色血细胞表达。CADM1促进肥大细胞与气道肌肉细胞和称为成纤维细胞的细胞的相互作用，使细胞粘附在一起，从而进行通信。关于CADM1如何发挥作用，或者它在气道肌肉和成纤维细胞上结合了什么，我们知之甚少。因此，在这个项目中，我们希望弄清楚CADM1如何调节肥大细胞功能，以及它如何与肥大细胞粘附的其他细胞类型相互作用。我们将使用我们实验室中已经建立的方法来解决这个问题。其中包括一种称为RNA干扰的专业技术，它可以抑制肥大细胞中产生CADM1的基因。该研究项目的结果将突出CADM1的影响可以控制的方法，并可能提供控制健康和疾病中肥大细胞功能的全新方法。

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.