Immunoglobulin Receptors and Immune Complex Processing in the Kidney

肾脏中的免疫球蛋白受体和免疫复合物处理

基本信息

批准号：
7787316
负责人：
SCOTT E WENDERFER
金额：
$ 13.43万
依托单位：
UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-15 至 2014-08-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7787316
关键词：
Acute Address Antigen-Antibody Complex Award Binding Blood Blood Vessels Cell Line Childhood Clinical Complement Cryoglobulinemia Development Diagnosis Dialysis procedure Disease Disease Management End stage renal failure Endothelial Cells Fc Receptor Fibrosis Foundations Future Gene Expression Glomerulonephritis Goals Health Sciences Immune Complex Diseases Immunoglobulin A Immunoglobulin G In Vitro Inflammation Inflammatory Injury Institutes Investigation Kidney Kidney Diseases Kidney Failure Kinetics Knockout Mice Molecular Medicine Mus Patients Process Publishing Renal function Research Resources Role Scientist Sepsis Serum Sickness Specificity Systemic Lupus Erythematosus Texas Universities Work cytokine immunoglobulin receptor in vivo in vivo Model mesangial cell mouse model novel pediatric department programs public health relevance receptor receptor internalization response

项目摘要

DESCRIPTION (provided by applicant): The candidate for this Clinical Scientist Development Award is a pediatric nephrologist who will use this work towards establishing an independent research program. The work will be conducted in the Institute of Molecular Medicine and in the Department of Pediatrics at The University of Texas Health Science Center at Houston. The goal of the proposed research is to define and study the role of a novel receptor for immune complexes on resident cells lining blood vessels within the mouse kidney. Immune complexes in the blood preferentially accumulate in the kidney in many inflammatory diseases, including systemic lupus erythematosus, IgA nephropathy, cryoglobulinemia, serum sickness and sepsis. Elucidating the mechanisms of accumulation and clearance is essential for accurately diagnosing and treating these forms of glomerulonephritis. CD300g is a novel immune complex receptor expressed on endothelial cells. The expression and function of CD300g will be studied in vitro and in vivo. Primary renal endothelial cell have been isolated and cultured, which serve as a unique resource. Specificity will be addressed using the available CD300g knock out mouse. The aims of the research plan are to 1) study the role of CD300g in immune complex binding by renal endothelial cells, 2) study the endothelial cell responses to immune complex binding in vitro, and 3) validate markers of CD300g activation by immune complexes in a mouse model of acute renal immune complex accumulation. Results will provide the foundation for future investigation on mechanisms of immune complex diseases of the kidney. PUBLIC HEALTH RELEVANCE: Immune complexes accumulate in the kidneys in 45-65% of patients with glomerulonephritis. Glomerulonephritis is an important cause of renal failure. This work will provide new avenues for approaching the diagnosis and management of these diseases, with potential to help preserve kidney function. This could reduce the burden of end stage renal disease and avoid the need for dialysis in a significant set of patients.

描述（由申请人提供）：该临床科学家发展奖的候选人是一名儿科肾病专家，他将利用这项工作来建立一个独立的研究项目。这项工作将在休斯顿德克萨斯大学健康科学中心的分子医学研究所和儿科部门进行。拟议研究的目标是定义和研究免疫复合物的新型受体对小鼠肾脏内血管内壁细胞的作用。在许多炎症性疾病中，血液中的免疫复合物优先积聚在肾脏中，包括系统性红斑狼疮、IgA 肾病、冷球蛋白血症、血清病和败血症。阐明积聚和清除机制对于准确诊断和治疗这些形式的肾小球肾炎至关重要。 CD300g是一种在内皮细胞上表达的新型免疫复合物受体。将在体外和体内研究CD300g的表达和功能。原代肾内皮细胞已被分离培养，是一种独特的资源。将使用可用的 CD300g 敲除小鼠来解决特异性问题。该研究计划的目的是 1) 研究 CD300g 在肾内皮细胞免疫复合物结合中的作用，2) 研究体外内皮细胞对免疫复合物结合的反应，以及 3) 验证肾内皮细胞中免疫复合物激活 CD300g 的标志物急性肾免疫复合物积聚的小鼠模型。结果将为未来研究肾脏免疫复合物疾病的机制奠定基础。公共卫生相关性：45-65% 的肾小球肾炎患者的肾脏中会积聚免疫复合物。肾小球肾炎是肾功能衰竭的重要原因。这项工作将为这些疾病的诊断和治疗提供新途径，并有可能有助于保护肾功能。这可以减轻终末期肾病的负担，并避免大量患者需要透析。