PHAGOCYTIC CELL FUNCTION

吞噬细胞功能

• 批准号: 3818118
• 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/3818118
• 关键词: blood disorder chemotherapy; blood disorder diagnosis; child (0-11); chronic granulomatous disease; complement receptor; cytochrome b; genetic disorder; genetic regulation; human subject; inflammation; lactoferrin; messenger RNA; metabolism disorder chemotherapy; metabolism disorder diagnosis; molecular pathology; neutrophil; phagocytes; phagocytic dysfunction; phagocytosis; relapse /recurrence; sex linked trait; tissue /cell culture

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.

该项目的主要目的是研究中性粒细胞