EOSINOPHIL PHENOTYPES IN CHRONIC EOSINOPHILIC PNEUMONIA

慢性嗜酸性肺炎是一种进行性肺部疾病。 表现为呼吸困难、夜间发热、盗汗、体重减轻、 肺泡-动脉供氧梯度增宽，这是一个典型的胸部 X线片和支气管肺泡灌洗(BAL)液嗜酸性粒细胞增多。这个 对这一疾病负有责任的代理人(S)尚未确定。因为我们 注意到低密度的嗜酸性粒细胞和升高的白介素5水平 特发性高嗜酸性粒细胞综合征患者血清和 色氨酸相关性嗜酸性粒细胞增多症-肌痛综合征，我们假设在 慢性嗜酸性肺炎，嗜酸性粒细胞寿命长， 通过暴露于一个或多个特定的监管机构而在功能上做好准备 细胞因子。嗜酸性粒细胞或同时发生，或作为后续事件 定位于与肺实质来源相关的肺实质 细胞因子，或对独立的并发刺激的反应。它是 确定嗜酸性粒细胞表型是细胞因子暴露和 体内引爆。基于这一发现，密度梯度沉积 将用于分离患者外周血中的嗜酸性粒细胞 慢性嗜酸性肺炎分为正常密度和低密度 亚群。分离的细胞将基于体外实验进行表型鉴定 存活率、定量LTC4生成、细胞毒性和膜 补体和免疫球蛋白受体的表达与黏附 分子。BAL液中的嗜酸性粒细胞将根据密度进行表型分析 和体外存活。将对血清和BAL液进行评估 维持嗜酸性粒细胞活性并调节其表型的能力。 如果存在细胞因子样活动，它们将被表征为基于 依赖于免疫决定因素，并在可能的范围内， 层析分析。如果这些因素出现在急性期 疾病，他们将在诱导缓解后重新检查。 最后，为了确定这些假定的嗜酸性粒细胞的细胞来源 调节性细胞因子，外周血和BAL液中的T淋巴细胞，以及 肺组织切片将通过RNA印迹分析和原位检测 杂交检测相关细胞因子基因表达的变化。 在临床缓解诱导后，细胞因子谱来自 相关的淋巴细胞群体将被重复。

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.