GALECTIN-2, AN ANIMAL LECTIN, IN ALLERGIC INFLAMMATION

Galectin-2（一种动物凝集素）在过敏性炎症中的作用

• 批准号: 2672735
• 负责人: FU-TONG LIU
• 金额: $ 21.68万
• 依托单位: LA JOLLA INSTITUTE FOR IMMUNOLOGY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-04-01 至 2000-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2672735
• 关键词: antibody receptor; chemical structure function; clinical research; disease /disorder model; epithelium; human subject; hypersensitivity; inflammation; laboratory mouse; lectin; leukocyte activation /transformation; macrophage; mast cell; model design /development; molecular pathology; protein sequence; tissue /cell culture

This research program deals with a protein that we have identified through its IgE-binding activity and extensively studied. This protein is now known as galectin-3, a member of a large family of beta-galactoside-binding animal lectins. We have accumulated a great deal of information on various aspects of galectin-3 which has allowed us to hypothesize that galectin-3 is a broad-spectrum amplifier of inflammatory response. We propose to continue to study the role of galectin-3 in inflammation by focusing on the following three specific aims. 1. Establishment of the function of galectin-3 inflammatory cells. We have shown various activities of galectin-3 by using exogenously added protein. THe role of galectin-3 in inflammation will be more firmly established by demonstrating that the endogenous lectin can participate in these activities. CO-culture systems in which galectin-3 secreted from macrophages and epithelial cells activates mast cells will be studied as examples. We will first establish conditions in which galectin-3 is released by inflammatory cells. The activity of galectin-3 i potentialteing the activation of inflammatory cells induced by other stimuli will also be investigated. Cells from galectin-3 mice will be used extensively for these analyses. 2. Development of animal models for establishing the role of galectin-3 inflammation. MOuse models of airway inflammation and cutaneous inflammation will be used to analyze the expression and secretion of galectin-3 in inflamatory responses. Galectin-3-deficient mice will be used to evaluate the role of galaectin-3 in airway and cutaneous inflammation. 3. Elucidation of the molecular basis for galectinn-3's activation of inflammatory cells. The realtionship between galectin-3's activation of mast cells and its recognition of Fc (epsilon) RI will be investigated. Molecular requirements for galectin-3's abilty to activates leukocytes will be delineated by focusing on galectin-3's self association property. Covalent galectin-3 dimers will be generated and compared with the mononomeric protein for various activities. AMino acid sequence in the amino-terminal region that is responsible for galectin-3's self association will be identified.

这项研究计划涉及一种蛋白质，我们已经通过 其IgE结合活性并被广泛研究。 这种蛋白质现在 称为半乳糖凝集素-3，是β-半乳糖苷结合蛋白大家族的成员， 动物凝集素 我们已经积累了大量的信息， 半乳糖凝集素-3的一些方面，这使我们能够假设半乳糖凝集素-3 是炎症反应的广谱放大器。 我们建议 继续研究半乳糖凝集素-3在炎症中的作用， 三个具体目标。 1. 半乳糖凝集素-3炎症细胞功能的建立。 我们 通过使用外源添加的半乳糖凝集素-3显示出多种活性 蛋白 半乳糖凝集素-3在炎症中的作用将更加坚定 通过证明内源性凝集素可以参与 这些活动。 共培养系统，其中半乳糖凝集素-3分泌自 巨噬细胞和上皮细胞激活肥大细胞将被研究， 例子. 我们将首先建立半乳糖凝集素-3被 由炎症细胞释放出来。 半乳糖凝集素-3的活性 增强由其他炎症因子诱导的炎症细胞的活化， 还将研究刺激。将使用来自半乳糖凝集素-3小鼠的细胞 在这些分析中， 2. 用于确定半乳糖凝集素-3作用的动物模型的开发 炎症 小鼠气道炎症和皮肤炎症模型 炎症将被用来分析表达和分泌 galectin-3在炎症反应中的作用。 半乳糖凝集素-3缺陷型小鼠将 用于评估半乳糖凝集素-3在气道和皮肤中的作用， 炎症 3. 半乳糖凝集素-3激活细胞凋亡的分子基础 炎症细胞 半乳糖凝集素-3激活细胞凋亡与细胞凋亡的关系 肥大细胞及其对Fc（γ）RI的识别将被研究。 半乳糖凝集素-3激活白细胞能力的分子要求将 通过关注galectin-3的自缔合特性来描绘。 将产生共价半乳糖凝集素-3二聚体，并将其与对照进行比较。 单聚体蛋白的各种活动。 氨基酸序列 负责半乳糖凝集素-3自身结合的氨基末端区域 将被识别。