Antioxidants attenuate endotoxin-induced activation of alveolar macrophages.
Antioxidants attenuate endotoxin-induced activation of alveolar macrophages.
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DOI：
10.1016/s0039-6060(05)80353-8
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发表时间：
1995-08
期刊：
影响因子：
3.8
通讯作者：
C. Mendez;I. García;R. Maier
中科院分区：
文献类型：
--
作者：
C. Mendez;I. García;R. Maier
背景内毒素（脂多糖[LPS]）刺激组织固定的巨噬细胞会诱导有毒氧化剂的产生。然而，最近的研究还表明细胞因子基因的信号转导途径和生理活性花生四烯酸代谢物的产生都发生了氧化还原变化。由于细胞因子和花生四烯酸代谢物会引发并维持有害的全身炎症反应，因此我们测试了抗氧化剂是否可以调节巨噬细胞的活化。方法通过支气管肺泡灌洗获得兔肺泡巨噬细胞，分离，用抗氧化剂维生素 E 或 N-乙酰半胱氨酸 (NAC) 处理，并用最佳剂量的 LPS (10 ng/ml) 刺激。对肿瘤坏死因子 (TNF)、促凝血活性和前列腺素 E2 进行测定。提取总细胞 RNA 进行 TNF 信使 RNA 的 Northern 印迹分析。结果将巨噬细胞暴露于抗氧化剂维生素 E 和 NAC 会抑制 TNF 产生、TNF 信使 RNA 积累、促凝血活性表达和前列腺素 E2 产生。结论 LPS 的巨噬细胞信号转导依赖于活性氧中间体的产生，该中间体可在脂膜水平（维生素 E）和细胞内水平被阻断（NAC）。这表明抗氧化剂在成人呼吸窘迫综合征和多器官衰竭综合征等以巨噬细胞过度激活为特征的疾病状态中具有潜在的治疗作用。
BackgroundEndotoxin (lipopolysaccharide [LPS]) stimulation of tissue-fixed macrophages induces the generation of toxic oxidants. However, recent studies also implicate redox changes in both the signal transduction pathways for cytokine genes and the generation of physiologically active arachidonic acid metabolites. Because cytokines and arachidonic acid metabolites initiate and perpetuate deleterious systemic inflammatory reponses, we tested whether macrophage activation could be modulated by antioxidants.MethodsRabbit alveolar macrophages were obtained by bronchoalveolar lavage, isolated, treated with the antioxidants vitamin E or N-acetylcysteine (NAC), and stimulated with an optimal dose of LPS (10 ng/ml). Assays were performed for tumor necrosis factor (TNF), procoagulant activity, and prostaglandin E2. Total cellular RNA was extracted for Northern blot analysis of TNF messenger RNA.ResultsExposure of the macrophage to the antioxidants vitamin E and NAC inhibited TNF production, accumulation of TNF messenger RNA, procoagulant activity expression, and prostaglandin E2production.ConclusionsMacrophage signal transduction of LPS is dependent on the generation of reactive oxygen intermediates that can be blocked both at the level of the lipid membrane (vitamin E) and at the intracellular level (NAC). This suggests a potential therapeutic role for antioxidants in disease states such as adult respiratory distress syndrome and multiple organ failure syndrome, which are characterized by excessive macrophage activation.