Parallel antitumor, granuloma-forming and tumor-necrosis-factor-priming activities of mycoloyl glycolipids fromNocardia rubra that differ in carbohydrate moiety: Structure—activity relationships
Parallel antitumor, granuloma-forming and tumor-necrosis-factor-priming activities of mycoloyl glycolipids fromNocardia rubra that differ in carbohydrate moiety: Structure—activity relationships
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红色诺卡氏菌中碳水化合物部分不同的菌酰糖脂的平行抗肿瘤、肉芽肿形成和肿瘤坏死因子引发活性：结构-活性关系
DOI：
10.1007/bf01742373
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
I. Yano
中科院分区：
文献类型：
--
作者：
Y. Natsuhara;S. Oka;K. Kaneda;Y. Kato;I. Yano
总结ICR小鼠多次静脉注射（30 µg，10次）来自红色诺卡氏菌的海藻糖二霉菌酸酯和葡萄糖单霉菌酸酯（含C36-48霉菌酸），对皮下植入的肉瘤-180（小鼠的同种异体肉瘤，肺、脾和肝中有显著肉芽肿形成）显示出显著的抗肿瘤作用。另一方面，除了葡萄糖单霉菌酸酯和海藻糖二霉菌酸酯之外的霉菌酰糖脂，如甘露糖或果糖霉菌酸酯，在小鼠中没有显示出显著的肿瘤消退或肉芽肿形成活性。红葡萄糖和葡萄糖单霉菌酸与C56-60分枝菌酸的红球菌也表现出独特的启动活性的肿瘤坏死因子（TNF）时，脂多糖从大肠杆菌作为一种引发剂。抗小鼠TNFα抗体与蛋白A琼脂糖凝胶结合后，小鼠血清中TNF活性几乎完全消失。与此相反，N.而BALB/c小鼠同系纤维肉瘤Meth-A对糖脂的敏感性低于肉瘤180。这些结果表明，葡萄糖或海藻糖分子的存在是必要的各种真菌酰糖脂之间的碳水化合物结构不同的免疫调节活性的表达。然而，由于脂多糖的给药基本上需要作为诱导TNF的引发剂，而不需要引发剂的抗肿瘤活性，TNF似乎不直接有助于我们的系统中的真菌酰糖脂的抗肿瘤活性。然而，肉芽肿形成，抗肿瘤和TNF-引发活性之间存在平行的结构-活性关系，表明碳水化合物部分和真菌酰残基的结构影响了初始步骤，如巨噬细胞活化，通常和深刻。
SummaryMultiple intravenous injections (30 µg, ten times) in ICR mice of trehalose dimycolate and glucose monomycolate fromNocardia rubra, containing C36–48 mycolic acids, showed a prominent antitumor effect on a subcutaneously implanted sarcoma-180, an allogeneic sarcoma of mice with a significant granuloma formation in lungs, spleen and liver. On the other hand, mycoloyl glycolipids other than glucose monomycolate and trehalose dimycolate, such as mannose or fructose mycolate, showed no significant activity for tumor regression or granuloma formation in mice.Trehalose dimycolate and glucose monomycolate fromN. rubra, and glucose monomycolate with C56–60 mycolic acids fromRhodococcus terrae also showed a distinctive priming activity for tumor necrosis factor (TNF), when lipopolysaccharide fromEscherichia coli was administered as an eliciting agent. The TNF activity in the sera of mice was abrogated almost completely by anti-(murine TNFα) antibody with protein-A—agarose. Again in contrast, mannose and fructose mycolate fromN. rubra and glucose monomycolate with C30–34 mycolic acids fromRhodococcus equi did not show such activities in mice.Meth-A, a syngeneic fibrosarcoma of BALB/c mice, was less sensitive to administration of glycolipids than sarcoma-180. These results indicated that the existence of a glucose or trehalose molecule was necessary for the expression of immunomodifying activities among various mycoloyl glycolipids differing in carbohydrate structure. However, since the administration of lipopolysaccharide was essentially required as an eliciting agent for the induction of TNF, while no eliciting agent was required for the antitumor activities, TNF does not seem to contribute directly to the antitumor activities of mycoloyl glycolipids in our systems. There was, however, a parallel structure-activity relationship among granuloma-forming, antitumor and TNF-priming activities, indicating that the structures of both the carbohydrate moiety and the mycoloyl residues influenced an initial step, such as macrophage activation, commonly and profoundly.
影响因子：
4.4
作者：
B. Beutler;I. Milsark;A. Cerami
通讯作者：
B. Beutler;I. Milsark;A. Cerami