Nuclear factor-kappa B is activated in alveolar macrophages from patients with acute respiratory distress syndrome
Nuclear factor-kappa B is activated in alveolar macrophages from patients with acute respiratory distress syndrome
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DOI：
10.1097/00003246-199608000-00004
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发表时间：
1996-08-01
影响因子：
8.8
通讯作者：
Abraham, E
中科院分区：
文献类型：
--
作者：
Schwartz, MD;Moore, EE;Abraham, E
目的：在急性呼吸窘迫综合征（ARDS）的实验模型、有ARDS风险的患者以及已确诊ARDS的患者中，促炎细胞因子的表达迅速增加。由于支气管肺泡灌洗液中存在多种细胞因子，在这些情况下可能存在一种共同的近端激活机制。在ARDS患者肺部表达增加的促炎细胞因子在其增强子/启动子区域具有转录调节蛋白的结合序列，如核因子 - κB（NF - κB）、核因子 - IL6（NF - IL6）、环磷酸腺苷反应元件结合蛋白、血清蛋白 - 1和激活蛋白 - 1。为了验证在ARDS情况下激活这些核转录调节因子中的一个或多个可能为多种细胞因子基因的同时表达提供一种共同机制这一假设，我们测量了ARDS患者和对照组肺泡巨噬细胞中这些因子的激活情况。
设计：前瞻性临床研究。
地点：一所大学医院和一所县医院的内科和外科重症监护病房。
患者：12名患者，6名已确诊ARDS，6名无肺损伤的对照患者。
干预措施：ARDS患者和对照组接受纤维支气管镜检查和支气管肺泡灌洗。从灌洗液中分离肺泡巨噬细胞并提取核蛋白。使用电泳迁移率变动分析测定转录因子NF - κB、NF - IL6、环磷酸腺苷反应元件结合蛋白、激活蛋白 - 1和血清蛋白 - 1的激活情况，然后对放射自显影凝胶进行光密度测定。
测量和主要结果：患者组在性别、年龄、吸烟情况、急性生理与慢性健康评估II评分、灌洗液量或灌洗标本中肺泡巨噬细胞数量方面无显著差异。对照组和ARDS患者之间的急性肺损伤评分以及动脉血氧分压（Pao₂）/吸入氧分数（Flo₂）比值有显著差异：0.46 ± 0.17对2.74 ± 0.14（p（此处似乎内容不完整）
Objective: The expression of proinflammatory cytokines is rapidly increased in experimental models of the acute respiratory distress syndrome (ARDS), in patients at risk for ARDS, and in patients with established ARDS. Because multiple cytokines are present in bronchoalveolar lavage fluid, a common, proximal activation mechanism may operate in these settings. The proinflammatory cytokines whose expression is increased in the lungs of patients with ARDS have binding sequences in their enhancer/promoter regions for transcriptional regulatory proteins, such as nuclear factor-kappa B (NF-kappa B), nuclear factor-IL6 (NF-IL6), cyclic adenosine monophosphate responsive element binding protein, serum protein-1, and activating protein-1. To test the hypothesis that activation of one or more of these nuclear transcriptional regulatory factors might provide a common mechanism for the simultaneous expression of multiple cytokine genes in the setting of ARDS, we measured activation of these factors in alveolar macrophages from patients with ARDS and from controls.Design: Prospective, clinical study.Setting: Medical and surgical intensive care units at a university hospital and a county hospital.Patients: Twelve patients, six with established ARDS and six control patients without lung injury.Interventions: Patients with ARDS and controls underwent fiberoptic bronchoscopy and bronchoalveolar ravage. Alveolar macrophages were isolated from ravage fluid and the nuclear proteins were extracted. Activation of transcriptional factors NF-kappa B, NF-IL6, cyclic adenosine monophosphate responsive element binding protein, activating protein-1, and serum protein-1 was determined using an electrophoretic mobility shift assay, followed by densitometry of the autoradiographed gels.Measurements and Main Results: There were no significant differences in gender, age, tobacco smoking, Acute Physiology and Chronic Health Evaluation II score, quantity of lavage fluid, or number of alveolar macrophages in lavage specimens in the patient groups. Acute Lung Injury score and the Pao(2)/Flo(2) ratio differed significantly between controls and ARDS patients: 0.46 +/- 0.17 vs. 2.74 +/- 0.14 (p