EVALUATION OF BASOPHIL INVOLVEMENT IN HUMAN DISEASE

嗜碱性粒细胞参与人类疾病的评估

• 批准号: 6055696
• 负责人: Lawrence B. Schwartz
• 金额: $ 19.45万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-01 至 2002-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6055696
• 关键词: asthma; atopic dermatitis; basophils; biomarker; clinical research; granule; human subject; hypersensitivity; immunoaffinity chromatography; immunocytochemistry; immunologic assay /test; intracellular membranes; laboratory mouse; leukocyte activation /transformation; membrane proteins; monoclonal antibody; nucleic acid sequence; protein sequence; rhinitis; technology /technique development; urticaria; urticaria pigmentosa

DESCRIPTION (Adapted from Investigator's abstract): Basophils and mast cells are major effector cells of immediate hypersensitivity reactions. In humans, mast cell involvement can be precisely identified by the presence of tryptase. For basophils, no such direct marker has been identified. The investigator hypothesizes that human basophil secretory granule proteins can be used as sensitive and specific markers of basophil involvement and that understanding the functions of such proteins will further our understanding of this cell type. The 2D7 mAb prepared by the investigator appears to recognize a basophil-specific component of the secretory granule. In skin during the late phase of an immediate hypersensitivity response, 2D7 immunohistochemistry reveals marked basophil involvement. Four specific aims are proposed. First, the 2D7 antigen will be purified by immunoaffinity chromatography and characterized. Second, basophils and deposits of activated basophils will be examined in human tissues using the 2D7 mAb, including skin in atopic dermatitis, chronic urticaria, and urticaria pigmentosa, nasal mucosa in allergic rhinitis and lung in asthma. Third, new mAbs against 2D7 antigen will be generated and used to develop a sandwich immunoassay. Fourth, basophil activation in various clinical situations will be assessed by measuring 2D7 antigen levels in biologic fluids. For example, the investigator hypothesizes that basophil-dependent anaphylaxis occurs in certain food-allergic reactions, and predict that 2D7 antigen, but not mast cell tryptase, will be elevated in the blood during such reactions. This research will provide novel and precise measures of basophil involvement in human diseases. This may enable more precise diagnostic criteria for flares of inflammation associated with atopic disease, facilitate selection of appropriate treatment, provide new prognostic information, and permit monitoring of inflammatory disease activity.

描述(改编自《调查者摘要》)：嗜碱性粒细胞和肥大 细胞是即刻超敏反应的主要效应细胞。在……里面 人类，肥大细胞的参与可以通过存在 类胰蛋白酶。对于嗜碱性粒细胞，还没有确定这样的直接标记。这个 研究人员假设人类嗜碱性粒细胞分泌颗粒蛋白可以 可作为嗜碱性粒细胞受累的敏感和特异标记物 了解这些蛋白质的功能将进一步加深我们对 这种细胞类型的。调查人员制备的2D7单抗似乎 识别分泌颗粒中嗜碱性粒细胞特有的成分。在皮肤上 在即刻超敏反应的晚期，2D7 免疫组织化学显示明显的嗜碱性粒细胞参与。四个具体的 提出了目标。首先，2D7抗原将通过以下方式提纯 并进行了免疫亲和层析和表征。第二，嗜碱性粒细胞和 激活的嗜碱性粒细胞沉积将在人体组织中使用 2D7单抗，包括特应性皮炎、慢性荨麻疹和 变应性鼻炎的变应性鼻炎、变应性鼻炎的鼻黏膜和哮喘的肺。 第三，将产生新的抗2D7抗原的单抗，并用于开发 三明治免疫分析。嗜碱性粒细胞在各种临床表现中的激活 将通过测量2D7抗原水平来评估情况 体液。例如，研究人员假设嗜碱性粒细胞依赖 过敏反应发生在某些食物过敏反应中，并预测2D7 抗原，但不是肥大细胞类胰蛋白酶，会在血液中升高 这样的反应。 本研究将为嗜碱性粒细胞的检测提供新的、准确的方法。 与人类疾病有关。这可以实现更精确的诊断 特应性疾病相关炎症爆发的标准， 促进选择适当的治疗，提供新的预后 信息，并允许监测炎症性疾病的活动。