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EVALUATION OF POLYMORPHONUCLEAR LEUKOCYTE SUBPOPULATIONS

多形核白细胞亚群的评估

基本信息

批准号：
3445646
负责人：
ROGER L BERKOW
金额：
$ 4.14万
依托单位：
UNIVERSITY OF ALABAMA AT BIRMINGHAM
依托单位国家：
美国
项目类别：
财政年份：
1984
资助国家：
美国
起止时间：
1984-09-30 至 1987-08-31
项目状态：
已结题

项目摘要

Subpopulations of human polymorphonuclear leukocytes (PMN) have been reported based on variations in rosetting to IgG coated erythrocytes, chemotaxis, binding of FMLP and membrane potential charge upon stimulation. No size differences have been noted among these subpopulations. Counterflow centrifugal elutriation (CCE) separates cells based on differences in size and density. Phase I of the proposal will evaluate volume dependent subpopulations of blood PMN isolated by CCE. Analysis of the early activation events of receptor ligand binding, membrane potential change, and alteration in membrane bound and cytosolic calcium upon stimulation will be performed. Superoxide has already been shown to be greater on a per cell basis in larger subgroups. Evaluation will be done to assess PMN subpopulation lag time and rate of the oxidative burst after stimulation. To determine if specific granule contents have a role in PMN subpopulations, Vit B12 binding protein will be analyzed. This analysis will assess the hypothesis that subpopulations of PMN exist in varying states of "readiness for activation". Phase II will assess the contribution of storage pool PMN to PMN subpopulations. PMN from bone marrow samples will be compared to peripheral blood PMN. PMN will also be isolated before and after a subcutaneous injection of epinephrine to assess the marginating pool of PMN. To evaluate the role of the spleen in storage of PMN and in volume dependent PMN subpopulations patients undergoing elective splenectomy will have PMN isolated before and after this procedure. These PMN will be compared to peripheral blood PMN by the methods utilized in Phase I. Analysis of shifts in subpopulations of the storage pool PMN will be performed utilizing CCE. Phase III will evaluate volume dependent PMN subpopulations of patients with altered host defenses. Wiskott-Aldrich syndrome, chronic granulomatous disease, burn patients, a patient with PMN lactoferrin deficiency, and sickle cell disease will be assessed. We believe that this information will aid in the understanding of PMN activation.

人类多形核白细胞（PMN）的亚群已被证实是根据对IgG包被的红细胞的玫瑰花结的变化报道，趋化性、FMLP结合和膜电位电荷刺激. 在这些之间没有注意到尺寸差异亚群逆流离心淘洗（CCE）分离细胞基于大小和密度的差异。该提案的第一阶段将评价通过CCE分离的血液PMN的体积依赖性亚群。受体配体结合的早期活化事件的分析，膜电位变化，以及膜结合和细胞溶质将进行刺激后的钙。超氧化物已经显示出在较大的子组中每个细胞的基础上更大。评价将进行评估PMN亚群的滞后时间和氧化速率，在刺激后爆裂。为了确定特定的颗粒含量是否具有分析Vit B12结合蛋白在PMN亚群中的作用。这分析将评估PMN亚群存在于不同的“激活准备状态”。第二阶段将评估储存池PMN对PMN亚群的贡献。骨PMN 将骨髓样本与外周血PMN进行比较。 PMN也将在皮下注射肾上腺素之前和之后分离，以评估 PMN的边缘池。评价脾脏在贮藏中的作用接受治疗的中性粒细胞和体积依赖性中性粒细胞亚群患者选择性脾切除术将在此之前和之后分离PMN procedure. 将这些PMN与外周血PMN进行比较，第一阶段使用的方法。人口亚群变化分析将使用CCE执行存储池PMN。第三阶段将评估宿主改变患者的体积依赖性PMN亚群的防御合作. Wiskott-Aldrich综合征，慢性肉芽肿病，烧伤患者，PMN乳铁蛋白缺乏症患者，镰状细胞将对疾病进行评估。我们认为，这些信息将有助于了解PMN激活。