HISTAMINE RELEASE FROM BEIGE MOUSE MAST CELLS

米色小鼠肥大细胞释放组胺

• 批准号: 3875589
• 负责人: J ZIMMERBERG
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 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/3875589
• 关键词: cell fusion; cell membrane; electron microscopy; exocytosis; extracellular matrix; granule; histamine release; intracellular; laboratory mouse; mast cell; membrane fusion; secretion; voltage /patch clamp

Mast cells of beige mice present with intracellular secretory granules of approximately 4 microns in diameter. When individual granules fuse with the plasma membrane during exocytosis, the cell surface area increases by 2-8 % for each fusion event (as measured by monitoring plasma membrane capacitance) and the granule diameters increase by 40%. These cells have been used in two independent but related projects. In the first project, these exocytotic pores were studied which form an aqueous pathway between the granule interior and the extracellular medium. The frequency histogram for occurrence of pores of given conductance is broad and independent of the frequency of the stimulating sine wave used to measure capacitance. Furthermore the frequency histogram is similar for two simultaneous but independent measurements of capacitance. In the second project, the physics-chemical nature of granule swelling was studied. Secretory granules generally contain a dehydrated, condensed polymer network or matrix that hydrates and swells upon release. In beige mouse mast cells, relative hydration is dependent upon the constituents of its ionic environment. Divalent cations reduce hydration whereas monovalent cations either have a negligible effect or increase the polymer hydration relative to the effects of distilled water alone. This size is critically dependent upon the solution present at the moment of initial swelling. This variable state behavior may have clinical relevance for Cystic Fibrosis (CF), a genetic disorder in which abnormally thick, dehydrated mucus secretions obstruct airways and pancreatic ducts. If the hydration state of the mucus is also irreversibly dependent on initial extracellular ionic conditions at the time of mucus secretion, then patients with CF may have mucus in an altered state due to the well known alteration in ionic composition of the extracellular composition.

米色小鼠的肥大细胞存在胞内分泌颗粒， 直径约为4微米。当单个颗粒与 胞吐过程中，细胞表面积增加2- 8% 对于每个融合事件（如通过监测质膜测量的 电容）和颗粒直径增加40%。这些细胞具有 它被用于两个独立但相关的项目。 在第一个项目中，研究了这些胞吐孔， 颗粒内部和细胞外介质之间的水通道。 给定电导率的孔隙出现的频率直方图为 宽且独立于用于 测量电容。此外，频率直方图对于两个 同时但独立的电容测量。 在第二个项目中，颗粒膨胀的物理化学性质是 研究了分泌颗粒通常含有脱水、浓缩的 在释放时水合和溶胀的聚合物网络或基质。穿米色 小鼠肥大细胞，相对水合作用取决于 离子环境。二价阳离子减少水合作用， 阳离子的影响可以忽略不计，或者增加聚合物的水合作用 相对于单独蒸馏水的效果。这一规模是至关重要的 这取决于初始溶胀时存在的溶液。这 可变状态行为可能与囊性纤维化有临床相关性 (CF)这是一种遗传性疾病， 分泌物阻塞气道和胰管。如果水化状态 粘液也不可逆地依赖于初始细胞外离子 在粘液分泌时的条件，那么CF患者可能有 由于众所周知的离子的改变，粘液处于改变的状态， 细胞外组分的组成。