MAST CELL GRANULES: STRUCTURE AND SECRETION

肥大细胞是组织中组胺的主要储存部位。 的 组胺储存在丰富的特异性分泌物中， 颗粒。 因此，肥大细胞的储存和颗粒的释放是至关重要的， 过敏性疾病如花粉热、荨麻疹、哮喘和 全身过敏反应 本研究的目的是阐明 颗粒中组胺的摄取和储存机制，以说明 负责颗粒分泌的分子事件 并识别细胞重组所涉及的过程 补充颗粒分泌后，细胞能够 反复分泌组胺等颗粒成分。 质子核磁共振将用于分析确定吸收的力， 组胺的储存 将研究咪唑C2-H和C4-H共振。 这两种光谱信号的化学位移和谱线增宽 细胞内组胺表达的质子与 使用分离肝素、天然肝素和 修饰的肝素蛋白复合物和颗粒基质。 的研究 分泌机制将集中在蛋白磷酸化： 磷酸化蛋白质和相关激酶的位点。 对于研究 的调节放电肥大细胞，细胞将被识别， 通过荧光激活细胞分选分离。 分离的肥大细胞 研究肥大细胞的合成、结构和分布 糜酶和肝素，组氨酸脱羧酶活性， 再生和未受刺激时组胺结合之间的差异 细胞 预计这些研究提供的信息 将增强能够阻断肿瘤的治疗剂的设计， 组胺和其他炎症介质的释放机制。

Mast cells are the primary storage site in tissues for histamine. The histamine is stored in and released from abundant specific secretory granules. Thus mast cell storage and release of granules are critical in the pathogenesis of allergic diseases such as hay fever, hives, asthma and systemic anaphylaxis. It is the aim of this research to elucidate the mechanism for uptake and storage of histamine in the granules, to specify the molecular events that are responsible for the secretion of the granules and to identify the processes involved in the reconstitution of the cells complement of granules after secretion by which the cell is able to repeatedly secrete histamine and other granule components repeatedly. Proton NMR will be used to analyze the forces that determine uptake and storage of histamine. Imidazole C2-H and C4-H resonances will be studied. The chemical shift and line broadening of the signals from these two protons expressed by intracellular histamine will be correlated with comparable charges in model systems using isolated heparin, native and modified heparin protein complexes, and granule matrices. Studies on the mechanism of secretion will concentrate on protein phosphorylation: the sites of phosphorylated proteins and the kinases responsible. For studies of regulation of discharged mast cells, the cells will be identified and separated by fluorescent-activated cell sorting. The separated mast cells will be studied for the synthesis, structure and distribution of mast cell chymase and heparin, the activity of histidine decarboxylase and differences between histamine binding in regenerating and unstimulated cells. It is anticipated that the information provided by these studies will enhance the design of therapeutic agents capable of interupting the mechanism for release of histamine and other inflammatory mediators.