PHAGOCYTIC CELL FUNCTION

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 和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。 本项目的范围还包括体外研究 这些遗传性疾病的模型系统， 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线的形式是由编码基因缺陷引起的， 细胞色素B的91 kDa亚基。 我们证明了不同的Kinetic 这种基因有不同的病变，因为有些患者没有 编码这种蛋白质的mRNA，其他人产生mRNA但不产生蛋白质， 而有些则产生功能缺陷蛋白质。 这些 观察表明，基因缺陷可能是一个新的突变， 突变发生在不同的位点。 我们有 最近显示有两种形式的细胞色素b阳性， 常染色体隐性遗传CGD。 最常见的形式是缺少一个47 kDa 胞浆蛋白，其磷酸化在活化中起作用 中性粒细胞的氧化代谢。我们已经证明， 导致中性粒细胞特异性颗粒缺乏病变是 一种分化阶段特异性髓系细胞损伤基因 调控 特别是，乳铁蛋白mRNA 在骨髓细胞中产生，但乳铁蛋白是合成的 正常情况下，鼻分泌物中的特定颗粒缺乏 患者

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-lined form results from a defect in the gene coding for the 91 kDa subunit of cytochrome b. We show that different kindreds have different lesions of this gene, in that some patients make no mRNA coding for this protein, others make mRNA but no protein, while some make a functionally defective protein. These observations suggest that the gene defect may be a new mutation in may kindreds and that mutations occur at different sites. We have recently shown that there are two forms of cytochrome b-positive, autosomal recessive CGD. The most common form is missing a 47 kDa cytosol protein, whose phosphorylation plays a role in activation of neutrophils oxidative metabolism. We have demonstrated that the lesion responsible for neutrophil specific granule deficiency is a differentiation stage specific lesion in myeloid cell gene regulation. In particular, there is a failure of lactoferrin mRNA production in myeloid cells, but lactoferrin is synthesized normally in nasal secretions of specific granule deficient patients.