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: 6171142
• 负责人: Lawrence B. Schwartz
• 金额: $ 19.89万
• 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/6171142
• 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（改编自研究者摘要）：嗜碱性粒细胞和肥大细胞 细胞是速发型超敏反应的主要效应细胞。 在 在人类中，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，没有这样的直接标记已被确定。 的 研究者推测，人嗜碱性粒细胞分泌颗粒蛋白可以 可用作嗜碱性粒细胞参与的敏感和特异性标志物， 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。 研究者制备的2D7 mAb似乎 识别分泌颗粒的嗜碱性粒细胞特异性成分。 皮肤 在速发型超敏反应的晚期，2D7 免疫组化显示嗜碱性粒细胞明显参与。 四个具体 提出了目标。 首先，2D7抗原将通过以下方法纯化： 免疫亲和层析并表征。 其次，嗜碱性粒细胞和 将使用免疫组织化学方法检测人体组织中活化嗜碱性粒细胞的沉积物。 2D7 mAb，包括特应性皮炎、慢性荨麻疹和 色素性荨麻疹、过敏性鼻炎的鼻粘膜和哮喘的肺。 第三，将产生针对2D7抗原的新的mAb并用于开发抗2D7抗原的单克隆抗体。 夹心免疫测定法 第四，嗜碱性粒细胞活化在各种临床 将通过测量生物制品中的2D7抗原水平来评估情况。 流体. 例如，研究者假设嗜碱性粒细胞依赖性 过敏反应发生在某些食物过敏反应，并预测2D7 抗原，但不是肥大细胞类胰蛋白酶，将在血液中升高， 这样的反应。 这项研究将提供新的和精确的措施嗜碱性粒细胞 参与人类疾病。 这可以实现更精确的诊断 与特应性疾病相关的炎症发作的标准， 有助于选择适当的治疗方法，提供新的预后 信息，并允许监测炎性疾病活动。