Role of Mast Cells in Inflammation and Immunity

肥大细胞在炎症和免疫中的作用

• 批准号: 6513033
• 负责人: Stephen Joseph Galli
• 金额: $ 38.87万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-08-20 至 2006-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6513033
• 关键词: angiogenesis; cell proliferation; cellular immunity; cytokine; epithelium; fibrosis; gene targeting; genetically modified animals; growth factor; inflammation; laboratory mouse; mast cell; microarray technology

DESCRIPTION: (Adapted from the investigator's abstract) The long term objective of this project is to understand to what extent, and by what mechanisms, mast cells (MCs) can influence the expression of many of the clinically important features of chronic inflammatory or immune responses. These features, that can occur in association with diverse adaptive or pathological responses, include the recruitment of leukocytes, the development of tissue fibrosis, the formation of blood vessels, and modulation of the proliferation of those cells that normally reside in the affected tissues, such as epithelial cells, fibroblasts, vascular endothelial cells, and the MC itself. In previous funding periods of this project, we have: 1) identified the MC as a potential source of TNF-a, IL6, MIP-la TGF-B, VPF/VEGF, and several other cytokines, chemokines and growth factors that can contribute to the local expression of inflammatory responses, and 2) developed new model systems for identifying and characterizing the specific roles of MCs during biological responses in vivo, including genetically MC-deficient Kit W/KitW-v mice that have been selectively repaired of their MC deficiency by the long-term adoptive transfer of immature MCs derived in vitro either from the bone marrow cells of the congenic normal (+/+) mice or from other populations of normal or genetically-altered hematopoietic or embryonic stem (ES) cells. We now propose to define in much greater detail the spectrum of protein products that can be secreted by MCs, to characterize mechanisms that can regulate the global or differential secretion of these products by this cell type, and to define the extent to which MCs and their secreted products contribute to the development of certain important features of persistent inflammatory or immune responses. Specifically, we wish to evaluate the hypothesis that the production of cytokines, chemokines and growth factors by MCs represents an important, and perhaps therapeutically accessible, link between the acute and chronic phases of many inflammatory or immune responses. We will: 1) further define the spectrum of cytokines, chemokines and growth factors that can be produced by human and mouse MCs and characterize how the production and release of these cytokines by MCs can be differentially regulated by immunological and non-immunological mechanisms; and 2) characterize certain specific roles of MCs and MC-derived cytokines, chemokines and growth factors in vivo, by analyzing representative inflammatory and immune responses that are associated with leukocyte infiltration and chronic tissue changes, such as epithelial proliferation, fibrosis and/or angiogenesis.

描述：（改编自研究者摘要）长期目的 这个项目的目的是了解在多大程度上，通过什么机制， 细胞（MCs）可以影响许多临床重要的 慢性炎症或免疫反应的特征。这些功能，可以 与多种适应性或病理性反应相关，包括 白细胞的募集，组织纤维化的发展， 血管的形成和这些细胞增殖的调节 通常存在于受影响的组织中，例如上皮细胞， 成纤维细胞、血管内皮细胞和MC本身。 在本项目以往的资助期内，我们已：1）确定管委会为 TNF-α、IL 6、MIP-1 α、TGF-β、VPF/VEGF和几种其它的潜在来源， 细胞因子、趋化因子和生长因子， 表达炎症反应，2）开发了新的模型系统， 识别和表征MC在生物学过程中的特定作用， 包括遗传性MC缺陷型Kit W/KitW-v小鼠， 已经被长期收养的人选择性地修复了他们的MC缺陷。 转移体外来源于骨髓细胞的未成熟MC， 同源正常（+/+）小鼠或来自其他正常或 遗传改变的造血或胚胎干（ES）细胞。 我们现在建议更详细地定义蛋白质的光谱 可以由MC分泌的产物，以表征可以 调节该细胞对这些产物的整体或差异分泌 类型，并定义MC及其分泌产物 有助于发展持久性有机污染物的某些重要特征， 炎症或免疫反应。具体而言，我们希望评估 假设细胞因子、趋化因子和生长因子的产生 MC代表了一个重要的，也许是治疗上可以达到的， 在许多炎症或免疫反应的急性和慢性阶段之间。 我们将：1）进一步明确细胞因子，趋化因子和生长的光谱 这些因子可以由人类和小鼠MC产生，并表征 MCs产生和释放这些细胞因子的能力可以是不同的， 由免疫和非免疫机制调节;和2） 表征MC和MC衍生的细胞因子、趋化因子 和生长因子，通过分析代表性的炎症和免疫 与白细胞浸润和慢性组织 变化，如上皮增殖、纤维化和/或血管生成。