EOSINOPHIL PHENOTYPES IN CHRONIC EOSINOPHILIC PNEUMONIA
慢性嗜酸性粒细胞肺炎中的嗜酸性粒细胞表型
基本信息
- 批准号:3769575
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:
- 资助国家:美国
- 起止时间:至
- 项目状态:未结题
- 来源:
- 关键词:
项目摘要
Chronic eosinophilic pneumonia is a progressive pulmonary disorder
characterized by dyspnea, evening fever, night sweats, weight loss, a
widened alveolar-arterial gradient for oxygen, a characteristic chest
radiographic, and bronchoalveolar lavage (BAL) fluid eosinophilia. The
agent(s) responsible for this disorder have not been defined. Because we
have noted hypodense eosinophils and increased levels of interleukin 5 in
the sera of patients with the idiopathic hypereosinophilic syndrome and
tryptophan-associated eosinophilia-myalgia syndrome, we postulate that in
chronic eosinophilic pneumonia, the eosinophils are rendered long-lived and
become functionally primed by exposure to one or more specific regulatory
cytokines. Either in parallel, or as a subsequent event, the eosinophils
localize to the pulmonary parenchyma in relation to the source of the
cytokine, or in response to an independent concurrent stimulus. It is
established that eosinophil phenotype is an index of cytokine exposure and
priming in vivo. Based upon this finding, density gradient sedimentation
will be used to separate peripheral blood eosinophils from patients with
chronic eosinophilic pneumonia into normodense and hypodense
subpopulations. The separated cells will be phenotyped based upon ex vivo
survival, quantitative LTC4 generation, cytotoxicity, and membrane
expression of selected complement and immunoglobulin receptors and adhesion
molecules. Eosinophils in BAL fluid will be phenotyped based upon density
and ex vivo survival. Serum and BAL fluid will be assessed for their
capacity to maintain eosinophil viability and regulated their phenotype.
If cytokine-like activities are present, they will be characterized based
upon immunologic determinants and, to the extent possible,
chromatographically. If such factors are present in the acute phase of the
disease, they will be reexamined after the induction of a remission.
Lastly, to determine the cell source of these putative eosinophil
regulatory cytokines, T lymphocytes in peripheral blood and BAL fluid, and
lung tissue sections will be examined by RNA blot analysis and in situ
hybridization for alterations in mRNA expression of relevant cytokines.
After the induction of a clinical remission, the cytokine profile from
relevant lymphocyte populations will be repeated.
慢性嗜酸性粒细胞性肺炎是一种进行性肺部疾病
特征为呼吸困难、夜间发热、盗汗、体重减轻,
肺泡-动脉血氧梯度增宽,
放射学检查和支气管肺泡灌洗(BAL)液嗜酸性粒细胞增多。 的
引起这种疾病的药物尚未确定。 因为我们
已经注意到低密度嗜酸性粒细胞和白细胞介素5水平的增加,
特发性嗜酸性粒细胞增多综合征患者的血清,
Eosinophilia-myalgia syndrome,我们假设,
慢性嗜酸性粒细胞性肺炎,嗜酸性粒细胞被赋予长寿命,
通过暴露于一个或多个特定的监管机构,
细胞因子 同时,或作为后续事件,嗜酸性粒细胞
定位于肺实质与源
细胞因子,或响应独立的并发刺激。 是
确定嗜酸性粒细胞表型是细胞因子暴露的指标,
体内预充。 基于这一发现,密度梯度沉积
将用于分离患者的外周血嗜酸性粒细胞,
慢性嗜酸性粒细胞性肺炎分为正常密度和低密度
亚群 分离的细胞将基于离体的表型分析。
存活、定量LTC 4生成、细胞毒性和膜
选择的补体和免疫球蛋白受体的表达和粘附
分子。 将根据密度对BAL液中的嗜酸性粒细胞进行表型分析
和离体存活率。 将评估血清和BAL液的
维持嗜酸性粒细胞活力并调节其表型的能力。
如果存在类尼古丁活性,则将基于
在免疫决定因素,并在可能的范围内,
色谱上。 如果这些因素存在于急性期,
疾病,他们将重新检查后,诱导缓解。
最后,为了确定这些假定的嗜酸性粒细胞的细胞来源,
调节细胞因子,外周血和BAL液中的T淋巴细胞,以及
肺组织切片将通过RNA印迹分析进行检查,
杂交用于相关细胞因子的mRNA表达的改变。
在诱导临床缓解后,来自
将重复相关的淋巴细胞群。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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WILLIAM F OWEN其他文献
WILLIAM F OWEN的其他文献
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{{ truncateString('WILLIAM F OWEN', 18)}}的其他基金
CYTOKINE-LIKE ACTIVITY THAT MEDIATES POST-MITOTIC PHENOTYPIC CHANGES
介导有丝分裂后表型变化的细胞因子样活性
- 批准号:
3844473 - 财政年份:
- 资助金额:
-- - 项目类别:
EOSINOPHIL PHENOTYPES IN CHRONIC EOSINOPHILIC PNEUMONIA
慢性嗜酸性粒细胞肺炎中的嗜酸性粒细胞表型
- 批准号:
3804153 - 财政年份:
- 资助金额:
-- - 项目类别:
CYTOKINE-LIKE ACTIVITY THAT MEDIATES POST-MITOTIC PHENOTYPIC CHANGES
介导有丝分裂后表型变化的细胞因子样活性
- 批准号:
3780525 - 财政年份:
- 资助金额:
-- - 项目类别:
CYTOKINE-LIKE ACTIVITY THAT MEDIATES POST-MITOTIC PHENOTYPIC CHANGES
介导有丝分裂后表型变化的细胞因子样活性
- 批准号:
3859310 - 财政年份:
- 资助金额:
-- - 项目类别:
CYTOKINE-LIKE ACTIVITY THAT MEDIATES POST-MITOTIC PHENOTYPIC CHANGES
介导有丝分裂后表型变化的细胞因子样活性
- 批准号:
3880344 - 财政年份:
- 资助金额:
-- - 项目类别:
FUNCTIONAL CHARACTERIZATION OF MONONUCLEAR HYPODENSE EOSINOPHILS
单核低密度嗜酸性粒细胞的功能表征
- 批准号:
3727366 - 财政年份:
- 资助金额:
-- - 项目类别:
EOSINOPHIL PHENOTYPES IN CHRONIC EOSINOPHILIC PNEUMONIA
慢性嗜酸性粒细胞肺炎中的嗜酸性粒细胞表型
- 批准号:
3747248 - 财政年份:
- 资助金额:
-- - 项目类别:
EOSINOPHIL PHENOTYPES IN CHRONIC EOSINOPHILIC PNEUMONIA
慢性嗜酸性粒细胞肺炎中的嗜酸性粒细胞表型
- 批准号:
3791695 - 财政年份:
- 资助金额:
-- - 项目类别:
CYTOKINE-LIKE ACTIVITY THAT MEDIATES POST-MITOTIC PHENOTYPIC CHANGES
介导有丝分裂后表型变化的细胞因子样活性
- 批准号:
3900576 - 财政年份:
- 资助金额:
-- - 项目类别:
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