牛磺罗定作为一种防腐和抗肿瘤药物，调节关键白细胞功能。
The Antiseptic and Antineoplastic Agent Taurolidine Modulates Key Leukocyte Functions.
机构信息
Department of Gastroenterology and Hepatology, Radboud University Medical Centre, Nijmegen, the Netherlands.
Department of Gastroenterology and Hepatology, Radboud University Medical Centre, Nijmegen, the Netherlands
出版信息
In Vivo. 2022 Sep-Oct;36(5):2074-2082. doi: 10.21873/invivo.12933.
BACKGROUND/AIM: Although taurolidine is known to exert a wide spectrum of biological actions, its effects on immune cells have not been characterized in detail. In this study, we investigated the ex vivo effects of taurolidine on relevant innate and adaptive immune cell functions.
MATERIALS AND METHODS
Leukocyte functions in whole blood were assessed following treatment with various taurolidine concentrations. Viability of peripheral blood mononuclear cells (PBMCs) and granulocytes was measured using the WST-1 assay. PBMC function was assessed by measuring TNFα and IFNγ production after stimulation with lipopolysaccharide (LPS) or Candida, respectively. Reactive oxygen species (ROS) production by granulocytes was measured in whole blood using luminol-enhanced chemiluminescence. Granulocyte degranulation and activation were evaluated by membrane expression of degranulation (CD63, CD66B) and adhesion markers (CD62L, CD11b) using immunofluorescent staining followed by flow-cytometric analysis.
RESULTS
Taurolidine decreased viability of PBMCs and granulocytes: after 2 h, IC concentrations were 500 and 520 μg/ml, respectively. Following prolonged exposure (≥24 h) of PBMCs, the IC concentrations declined to 40 μg/ml. PBMC cytokine production significantly decreased at taurolidine concentrations below the cytotoxic threshold, whereas no changes in ROS production were observed. The expression of all granulocyte adhesion and degranulation markers increased at concentrations higher than 500 μg/ml (the cytotoxic level of taurolidine).
CONCLUSION
Taurolidine exhibits a dose- and time-dependent cytotoxicity toward PBMCs and granulocytes. The effects on PBMCs, as exemplified by a decrease in cytokine production, occurred below the toxic threshold, whereas granulocyte function (ROS production) remained unchanged at these taurolidine concentrations. Granulocyte activation and degranulation markers only increased at cytotoxic taurolidine concentrations.
背景/目的：虽然已知牛磺罗定具有广泛的生物学作用，但尚未详细描述其对免疫细胞的影响。在这项研究中，我们研究了牛磺罗定对相关固有和适应性免疫细胞功能的体外影响。
材料和方法
用各种牛磺罗定浓度处理全血后，评估白细胞功能。使用 WST-1 测定法测量外周血单核细胞（PBMC）和粒细胞的活力。通过测量分别用脂多糖（LPS）或念珠菌刺激后产生的 TNFα和 IFNγ来评估 PBMC 功能。使用发光增强化学发光法在全血中测量粒细胞产生的活性氧物质（ROS）。通过免疫荧光染色和流式细胞术分析，评估粒细胞脱颗粒和活化的膜表达（脱颗粒（CD63、CD66B）和粘附标志物（CD62L、CD11b）。
结果
牛磺罗定降低 PBMC 和粒细胞的活力：2 小时后，IC 浓度分别为 500 和 520 μg/ml。PBMC 长时间暴露（≥24 小时）后，IC 浓度降至 40 μg/ml。在低于细胞毒性阈值的牛磺罗定浓度下，PBMC 细胞因子产生显著减少，而 ROS 产生没有变化。高于 500 μg/ml（牛磺罗定的细胞毒性水平）时，所有粒细胞粘附和脱颗粒标志物的表达均增加。
结论
牛磺罗定对 PBMC 和粒细胞表现出剂量和时间依赖性细胞毒性。对 PBMC 的影响（例如细胞因子产生减少）发生在毒性阈值以下，而在这些牛磺罗定浓度下，粒细胞功能（ROS 产生）保持不变。仅在细胞毒性牛磺罗定浓度下，粒细胞活化和脱颗粒标志物才增加。
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