PHAGOCYTIC CELL FUNCTION

吞噬细胞功能

• 批准号: 3821970
• 负责人: J I GALLIN
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3821970
• 关键词: blood disorder chemotherapy; blood disorder diagnosis; chemotaxis; child (0-11); chronic granulomatous disease; cytochrome b; electron microscopy; genetic regulation; granule; human subject; inflammation; interferons; leukocyte disorder; membrane activity; metabolism disorder chemotherapy; metabolism disorder diagnosis; monocyte; neutrophil; phagocytes; phagocytic dysfunction; phagocytosis

The major objective of this project has been to study neutrophil function in health and disease. Determination of the biochemical and genetic basis of inherited diseases affecting phagocytes and associated with recurrent infections, and the diagnosis and treatment of these diseases is a major component of this project. Also within the scope of this project is the study of in vitro model systems of these inherited diseases using preparations of phagocytic cells derived from normal volunteers and patients. We have shown that Chronic Granulomatous Diseases (CGD) are a heterogeneous group of diseases resulting from absent H202 production by phagocytes, associated with recurrent infections. The X-linked form is usually associated with absence of cytochrome b from phagocytes, while the autosomal form does not lack cytochrome b. We have documented exceptions to this, and even an autosomal dominant form. We have found that Interferon gamma treatment of monocytes from some CGD patients (usually autosomal form) results in normalization of H202 production, suggesting that this may be a treatment modality. Granuloma formation in CGD may cause obstructions, but our studies indicate good outcome with steroid therapy. An in vitro model of granuloma formation using monocytes suggests that CGD patients may not effectively destroy inflammatory mediators such as LTB4, leading to exuberant cellular reaction and granuloma. We have been studying a patient with deficiency of specific granules. Further study indicated the absence of defensins, bactericidal proteins present in azurophil granules. Although this patient also fails to make lactoferrin, Southern blots indicate that he has the gene for this protein. This disease may be a defect in gene regulation.

该项目的主要目的是研究中性粒细胞 在健康和疾病中发挥作用。 生化测定 以及影响吞噬细胞的遗传性疾病的遗传基础， 与复发性感染有关，诊断和 治疗这些疾病是该项目的一个主要组成部分。 本项目还包括体外模型研究 这些遗传性疾病的系统使用制剂， 来自正常志愿者和患者的吞噬细胞。 我们 慢性肉芽肿病（CGD）是一种 H2O2缺乏导致的异质性疾病 由吞噬细胞产生，与复发性感染有关。 X连锁形式通常与缺乏 吞噬细胞的细胞色素B，而常染色体的形式 不缺乏细胞色素B。 我们记录了一些例外情况， 甚至是常染色体显性遗传 我们发现 来自某些CGD的单核细胞的干扰素γ处理 患者（通常为常染色体形式）导致H2O2正常化 生产，这表明这可能是一种治疗方式。 CGD中肉芽肿的形成可能会导致阻塞，但我们的 研究表明类固醇治疗效果良好。 体外 使用单核细胞的肉芽肿形成模型表明， CGD患者可能无法有效地破坏炎症 介质如LTB4，导致旺盛的细胞反应 和肉芽肿。 我们一直在研究一个 特殊的颗粒。 进一步的研究表明， 防御素，存在于嗜天青颗粒中的杀菌蛋白。 虽然这名患者也无法制造乳铁蛋白，但Southern 印迹显示他有这种蛋白质的基因 这种疾病 可能是基因调控的缺陷