PHAGOCYTIC CELL FUNCTION

吞噬细胞功能

• 批准号: 3809559
• 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/3809559
• 关键词: Aspergillus; aspergillosis; blood disorder chemotherapy; blood disorder diagnosis; child (0-11); chronic granulomatous disease; cytochrome b; gene expression; genetic disorder; human subject; inflammation; metabolism disorder chemotherapy; metabolism disorder diagnosis; molecular pathology; mycosis; neutrophil; nucleic acid probes; opportunistic infections; phagocytes; phagocytic dysfunction; phagocytosis; relapse /recurrence; sex linked trait; tissue /cell culture

The purpose of this project is to determine the genetic basis of inherited diseases affecting neutrophil function and associated with recurrent infections, and diagnosis and treatment of such disorders. Chronic Granulomatous Diseases of Childhood (CGD) are a group of diseases with common phenotype including absent H202 production by phagocytes, recurrent infections, and granuloma formation. We have documented the prevalence of the four distinct genetic forms of CGD (60% X-linked defect in cytochrome b558 gp9l-phox subunit; 5% autosomal recessive (AR) defect in cytochrome p22-phox subunit; 30% AR affecting p47-phox cytosolic oxidase factor; 5% AR affecting p67phox cytosolic factor). Studies of p67-phox gene structure reveals two normal allelic HinDIII restriction enzyme patterns which will be useful in prenatal diagnosis and mapping chromosome 1q25 region. In other studies expression of p47-phox by retroviral vector provides an important tool for eventual genetic reconstitution of this form of CGD. We have documented the effectiveness of low dose steroids in management of obstructive granulomas of gastrointestinal and urinary system. We have documented the importance of early surgical extirpation of pulmonary aspergillus infections and drainage of liver abscesses. Review of our CGD patients' histories indicated that prophylactic trimethaprim-sulfa reduces bacterial infections without causing an increase in fungal infection. Using an in vitro assay of fungal killing by neutrophils, we have documented that a small number of normal neutrophils act synergistically with a larger number of CGD neutrophils to kill aspergillus hyphae providing a rationale for use of granulocyte transfusions in infected CGD patients.

该项目的目的是确定遗传的遗传基础 影响中性粒细胞功能并与复发相关的疾病 感染以及此类疾病的诊断和治疗。慢性的 儿童肉芽肿性疾病 (CGD) 是一组具有以下特征的疾病： 常见表型包括吞噬细胞不产生 H202、复发性 感染和肉芽肿形成。我们记录了以下情况的流行情况 CGD 的四种不同遗传形式（细胞色素中 60% 的 X 连锁缺陷） b558 gp9l-phox 亚基； 5% 细胞色素常染色体隐性 (AR) 缺陷 p22-phox 亚基； 30% AR 影响 p47-phox 胞质氧化酶因子； 5% 应收率 影响 p67phox 胞质因子）。 p67-phox基因结构的研究 揭示了两种正常的等位基因 HinDIII 限制酶模式，这将 可用于产前诊断和绘制染色体 1q25 区域图谱。在 其他研究通过逆转录病毒载体表达 p47-phox 提供了 最终对这种形式的 CGD 进行基因重建的重要工具。我们 已经记录了低剂量类固醇在管理中的有效性 胃肠道和泌尿系统的阻塞性肉芽肿。我们有 记录了早期手术摘除肺结核的重要性 曲霉菌感染和肝脓肿引流。我们的 CGD 回顾 患者的病史表明，预防性使用磺胺甲氧苄啶可减少 细菌感染，但不会增加真菌感染。使用 中性粒细胞杀死真菌的体外测定，我们记录了 少量正常中性粒细胞与较大数量的中性粒细胞协同作用 杀死曲霉菌丝的 CGD 中性粒细胞数量提供了理论依据 用于感染 CGD 患者的粒细胞输注。