ROLE OF ADHESION MOLECULES IN MAST CELL AND BASOPHILS FUNCTION

粘附分子在肥大细胞和嗜碱性粒细胞功能中的作用

• 批准号: 6104661
• 负责人: R P SIRAGANIAN
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6104661
• 关键词: basophils; biological signal transduction; cell adhesion molecules; extracellular matrix proteins; fibronectins; inflammation; integrins; mast cell; protein kinase; receptor binding; tissue /cell culture

The inflammatory response is characterized by the accumulation of extracellular matrix proteins at sites of injury. Mast cells and basophils accumulate at such inflammatory sites and play a role by releasing an array of mediators. Basophils and mast cells have surface adhesion receptors that are involved in the binding of these cells to other cells or to the extracellular matrix. Such integrin mediated adherence of cells to fibronectin stimulates cell spreading and generates intracellular signals. Previously we observed that the RBL-2H3 cells bind through integrin receptors to surfaces coated with fibronectin; this results in changes in the cytoskeleton, cell spreading and a redistribution of the granules to the periphery of the cells. These changes result in the tyrosine phosphorylation of several proteins including the focal adhesion kinase, pp125FAK (FAK) and in enhanced secretion by the cells. FAK is a widely expressed protein tyrosine kinase that localizes with integrins and several proteins to intracellular sites where cells are in contact with the extracellular matrix. FAK also becomes tyrosine phosphorylated in response to the activation of various receptors including FceRI and antigen receptors on T-cells. In studies during this year we have continued exploring the interaction of intracellular signals generated by adhesion and immune receptor activation.

炎症反应的特征在于 细胞外基质蛋白在损伤部位的积累。桅杆 细胞和嗜碱性粒细胞聚集在这些炎症部位， 通过释放一系列调解人来发挥作用。嗜碱性粒细胞和肥大细胞 有表面粘附受体参与结合 这些细胞与其他细胞或细胞外基质结合。这种整合素 细胞对纤连蛋白的介导粘附刺激细胞铺展 并产生细胞内信号。之前我们观察到， RBL-2 H3细胞通过整联蛋白受体与包被的表面结合 与纤连蛋白;这导致细胞骨架，细胞 分散和再分布的颗粒的周边 细胞。这些变化导致酪氨酸磷酸化， 包括粘着斑激酶pp 125 FAK在内的几种蛋白质 (FAK)以及细胞分泌的增强。FAK是一个广泛的 表达的蛋白酪氨酸激酶，其定位于整联蛋白， 几种蛋白质到细胞内的位点，在那里细胞与 细胞外基质FAK也被酪氨酸磷酸化 响应于包括FceRI在内的各种受体的激活 和T细胞上的抗原受体。在今年的研究中， 继续探索细胞内信号的相互作用 由粘附和免疫受体激活产生。