GALECTIN-2, AN ANIMAL LECTIN, IN ALLERGIC INFLAMMATION

这个研究项目涉及一种蛋白质，我们通过 其免疫球蛋白E结合活性得到了广泛的研究。这种蛋白质现在是 被称为Galectin-3，是β-半乳糖苷结合大家族的成员 动物凝集素。我们已经积累了大量关于各种类型的信息 Galectin-3的某些方面使我们可以假设Galectin-3 是炎症反应的广谱放大器。我们建议 继续研究Galectin-3在炎症中的作用 遵循三个具体目标。 1.半乳糖凝集素-3炎症细胞功能的建立我们 通过外源添加的方法显示了Galectin-3的各种活性 蛋白。Galectin-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。分泌Galectin-3的共培养体系 巨噬细胞和上皮细胞激活肥大细胞将被研究为 举个例子。我们将首先建立Galectin-3存在的条件 由炎性细胞释放。半乳糖凝集素-3的活性 增强异丙肾上腺素诱导的炎症细胞活化 刺激物也将被调查。来自Galectin-3小鼠的细胞将被使用 广泛用于这些分析。 2.半乳糖凝集素-3作用动物模型的建立 发炎。小鼠呼吸道炎症和皮肤炎症模型的建立 炎症将被用来分析表达和分泌 Galectin-3在炎症反应中的作用Galectin-3缺陷小鼠将是 用于评价Galaectin-3在呼吸道和皮肤中的作用 发炎。 3.半乳糖凝集素-3‘-S活化的分子基础 炎性细胞。半乳糖凝集素-3‘-S激活血管内皮细胞的关系 肥大细胞及其对Fc(Epsilon)RI的识别将被研究。 半乳糖凝集素-3‘S激活白细胞功能的分子要求 重点研究了半乳糖凝集素-3‘S的自缔合性质。 将产生共价Galectin-3二聚体，并与 参与各种活动的单体蛋白质。蛋白质中的氨基酸序列 负责Galectin-3‘S自结合的氨基末端区域 将会被确认。

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.