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胞壁酰二肽诱导的非特异性宿主抗感染抵抗力的刺激作用。

Stimulation of nonspecific host resistance to infection induced by muramyldipeptides.

作者信息

Matsumoto K, Ogawa H, Nagase O, Kusama T, Azuma I

出版信息

Microbiol Immunol. 1981;25(10):1047-58. doi: 10.1111/j.1348-0421.1981.tb00111.x.

DOI:10.1111/j.1348-0421.1981.tb00111.x
PMID:7031443
Abstract

The effect of muramyldipeptide (MDP), N-acetylmuramyl-L-alanyl-D-isoglutamine [MDP(Ala)], and its analogs on bacterial infection was studied using the experimental model of sepsis infection in mice. Injection of MDP(Ala) gave mice definitive protection against E. coli infection, but only partial protection against P. aeruginosa or K. pneumoniae infection. Several factors influencing the protective activity of MDP(Ala) on E. coli infection were studied, and it was demonstrated that the activity was induced by various routes of administration of MDP(Ala), including the oral route, and was markedly influenced by the bacterial inoculum size. It was also shown that the effective dose of MDP(Ala) was 100 micrograms per mouse for intraperitoneal, intravenous or subcutaneous injections and 1,000 microgram per mouse when administered orally. Furthermore, the optimal interval between MDP-treatment and infection was 24 hr when the treatment was carried out before infection. Clearance of bacterial cells in blood was observed after E. coli infection in mice treated with MDP(Ala). The efficacy of MDP(Ala) and two analogs, N-acetylmuramyl-L-valyl-D-isoglutamine [MDP(Val)] and N-acetylmuramyl-L-seryl-D-isoglutamine [MDP (Ser)], was evaluated for the E. coli infection; MDP(Val) was proven to be slightly less active than MDP(Ala), and MDP(Ser) to be the least effective, although MDP(Val) or MDP(Ser) was reported to have higher adjuvanticity than MDP (Ala) for the development of delayed-type hypersensitivity.

摘要

利用小鼠脓毒症感染实验模型,研究了胞壁酰二肽(MDP)、N-乙酰胞壁酰-L-丙氨酰-D-异谷氨酰胺[MDP(Ala)]及其类似物对细菌感染的影响。注射MDP(Ala)能使小鼠对大肠杆菌感染获得确切保护,但对铜绿假单胞菌或肺炎克雷伯菌感染仅提供部分保护。研究了影响MDP(Ala)对大肠杆菌感染保护活性的几个因素,结果表明,MDP(Ala)通过包括口服途径在内的各种给药途径均可诱导该活性,且该活性受细菌接种量的显著影响。还表明,MDP(Ala)腹腔内、静脉内或皮下注射的有效剂量为每只小鼠100微克,口服时为每只小鼠1000微克。此外,当在感染前进行治疗时,MDP治疗与感染之间的最佳间隔为24小时。在用MDP(Ala)治疗的小鼠中,观察到大肠杆菌感染后血液中细菌细胞的清除情况。评估了MDP(Ala)及其两种类似物N-乙酰胞壁酰-L-缬氨酰-D-异谷氨酰胺[MDP(Val)]和N-乙酰胞壁酰-L-丝氨酰-D-异谷氨酰胺[MDP(Ser)]对大肠杆菌感染的疗效;事实证明,MDP(Val)的活性略低于MDP(Ala),而MDP(Ser)的效果最差,尽管据报道MDP(Val)或MDP(Ser)在迟发型超敏反应的发生方面比MDP(Ala)具有更高的佐剂活性。

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