Ogawa T, Kotani S, Tsujimoto M, Kusumoto S, Shiba T, Kawata S, Yokogawa K
Infect Immun. 1982 Feb;35(2):612-9. doi: 10.1128/iai.35.2.612-619.1982.
Cell walls isolated from four bacterial species (Streptococcus pyogenes, Lactobacillus plantarum, Streptomyces gardneri, and Nocardia corynebacteriodes), which exhibited the adjuvant effect of stimulating cellular and humoral immune responses against ovalbumin in guinea pigs, caused the slow-starting and long-lasting contraction of guinea pig ileal strips suspended in Tyrode solution. In contrast to these cell walls active in immunoadjuvancy, those isolated from five bacterial species (Micrococcus lysodeikticus, Staphylococcus epidermidis, Arthrobacter atrocyaneus, Corynebacterium insidiosum, and Ampullariella regularis), which lacked immunoadjuvancy at least in intact walls, caused no or very weak contraction of the ileal strips. Further study demonstrated that both a monomer and a polymer of disaccharide-stem peptides, which were obtained by enzymatic degradation of S. epidermis cell wall peptidoglycans, displayed similar contractile effects. It was finally revealed that guinea pig ileum strips showed a definite contractile response to N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP) and 6-O-stearoyl- and 6-O-(2-tetradecylhexadecanoyl)-MDPs, but not to their analogs, whose C-terminal amino acid was L-isoglutamine or D-isoasparagine in place of D-isoglutamine and which lacked adjuvancy. 6-O-(3-Hydroxy-2-docosylhexacosanoyl)-MDP, on the other hand, caused a slow and lasting relaxation of the ileum strips, but its L-isoglutamine and D-isoasparagine analogs did not.
从四种细菌(化脓性链球菌、植物乳杆菌、加德纳链霉菌和类棒状诺卡氏菌)中分离得到的细胞壁,在豚鼠体内表现出刺激针对卵清蛋白的细胞免疫和体液免疫反应的佐剂效应,能使悬浮在台氏液中的豚鼠回肠肌条出现缓慢起始且持久的收缩。与这些具有免疫佐剂活性的细胞壁形成对比的是,从五种细菌(溶壁微球菌、表皮葡萄球菌、蓝黑色节杆菌、阴险棒状杆菌和规则瓶囊霉)中分离得到的细胞壁,至少在完整状态下缺乏免疫佐剂活性,对回肠肌条没有或仅有非常微弱的收缩作用。进一步研究表明,通过对表皮葡萄球菌细胞壁肽聚糖进行酶促降解得到的二糖 - 茎肽的单体和聚合物,表现出相似的收缩效应。最终发现,豚鼠回肠肌条对N - 乙酰胞壁酰 - L - 丙氨酰 - D - 异谷氨酰胺(MDP)以及6 - O - 硬脂酰 - 和6 - O -(2 - 十四烷基十六酰)- MDP有明确的收缩反应,但对其类似物没有反应,这些类似物的C末端氨基酸是L - 异谷氨酰胺或D - 异天冬酰胺而非D - 异谷氨酰胺且缺乏佐剂活性。另一方面,6 - O -(3 - 羟基 - 2 - 二十二烷基二十六酰)- MDP会使回肠肌条出现缓慢且持久的舒张,但它的L - 异谷氨酰胺和D - 异天冬酰胺类似物则不会。