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牛磺罗定,一种抗脂多糖剂,具有由氨基酸牛磺酸介导的免疫调节特性。

Taurolidine, an antilipopolysaccharide agent, has immunoregulatory properties that are mediated by the amino acid taurine.

作者信息

Watson R W, Redmond H P, Mc Carthy J, Bouchier-Hayes D

机构信息

Department of Surgery, RCSI, Beaumont Hospital, Dublin, Ireland.

出版信息

J Leukoc Biol. 1995 Sep;58(3):299-306. doi: 10.1002/jlb.58.3.299.

Abstract

Taurolidine has bactericidal and antilipopolysaccharide properties. It is broken down into the amino acid taurine, which has been shown to modulate intracellular calcium activity, a critical component in the priming and activation of macrophages and polymorphonuclear leukocytes. We hypothesized that taurolidine may function to enhance immune activity in these cells. The aim of this study was to investigate the immunological effects of taurolidine and correlate findings with survival after a septic challenge in a murine model. Study 1: CD-1 mice underwent cecal ligation and puncture, were randomized to receive taurolidine (200 mg/kg body weight/i.p.) or saline control, and studied for end point survival. Study 2: CD-1 mice were randomized to receive taurolidine (200 mg/kg body weight/i.p.) or saline control. Peritoneal macrophages (PM luminal diameters) were assessed for O2-, NO, tumor necrosis factor-alpha (TNF-alpha), CD11b, phagocytosis, and PMN influx. O2-, TNF-alpha, CD11b expression, and phagocytosis were significantly increased in the taurolidine group. Study 3: PM luminal diameters were cultured in vitro +/- 0.5 mg/ml taurolidine and PM luminal diameter antimicrobial function assessed (O2-, NO, TNF-alpha, and phagocytosis). O2-, TNF-alpha, and phagocytosis were significantly increased, whereas NO was reduced. Study 4: PM luminal diameters were also cultured with taurine (0.5 mg/ml). Similar increase in O2-, TNF-alpha, and phagocytosis were identified. Intracellular PM luminal diameter [Ca2+] was also assessed and increases in free, unbound intracellular [Ca2+] occurred after taurine culture. Thus, in addition to its bactericidal and antilipopolysaccharide activity, taurolidine primes PM luminal diameters for enhanced antimicrobial activity and these effects appear mediated by the amino acid taurine.

摘要

替考拉宁具有杀菌和抗脂多糖特性。它会分解为氨基酸牛磺酸,研究表明牛磺酸可调节细胞内钙活性,而细胞内钙活性是巨噬细胞和多形核白细胞启动和激活的关键组成部分。我们推测替考拉宁可能具有增强这些细胞免疫活性的作用。本研究旨在探讨替考拉宁的免疫效应,并将研究结果与小鼠模型脓毒症激发后的生存率相关联。研究1:对CD-1小鼠进行盲肠结扎和穿刺,随机分为两组,分别接受替考拉宁(200毫克/千克体重/腹腔注射)或生理盐水对照,并观察终点生存率。研究2:将CD-1小鼠随机分为两组,分别接受替考拉宁(200毫克/千克体重/腹腔注射)或生理盐水对照。评估腹腔巨噬细胞(PM管腔直径)的超氧阴离子(O2-)、一氧化氮(NO)、肿瘤坏死因子-α(TNF-α)、CD11b、吞噬作用以及多形核白细胞(PMN)流入情况。替考拉宁组的O2-、TNF-α、CD11b表达和吞噬作用均显著增加。研究3:将PM管腔直径在体外培养,添加或不添加0.5毫克/毫升替考拉宁,并评估PM管腔直径的抗菌功能(O2-、NO、TNF-α和吞噬作用)。O2-、TNF-α和吞噬作用显著增加,而NO减少。研究4:PM管腔直径也与牛磺酸(0.5毫克/毫升)一起培养。发现O2-、TNF-α和吞噬作用有类似增加。还评估了细胞内PM管腔直径的[Ca2+],牛磺酸培养后细胞内游离、未结合的[Ca2+]增加。因此,除了其杀菌和抗脂多糖活性外,替考拉宁还能使PM管腔直径启动以增强抗菌活性,这些作用似乎是由氨基酸牛磺酸介导的。

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