EOSINOPHIL PHENOTYPES IN CHRONIC EOSINOPHILIC PNEUMONIA

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，或响应于独立的并发刺激。 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。

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.