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与多聚(DL-丙氨酰)-聚(L-赖氨酸)载体偶联后,一种无活性的胞壁酰二肽衍生物在体外对巨噬细胞的刺激作用。

Macrophage stimulation in vitro by an inactive muramyl dipeptide derivative after conjugation to a multi-poly(DL-alanyl)-poly(L-lysine) carrier.

作者信息

Galelli A, Le Garrec Y, Chedid L, Lefrancier P, Derrien M, Level M

出版信息

Infect Immun. 1980 Apr;28(1):1-5. doi: 10.1128/iai.28.1.1-5.1980.

Abstract

It has been previously reported that N-acetyl-muramyl-L-alanyl-D-isoglutamine (MDP), which represents the minimal structure that can substitute for mycobacteria in Freund complete adjuvant, activated macrophages in vitro and in vivo. In the present study we show that, in contrast to MDP, the nonadjuvant MDP(DD) stereoisomer has no effect on cytostatic activity of thioglycolate-induced macrophages as measured by uptake of [3H]thymidine. However, surprisingly, after conjugation to an inert carrier, multi-poly(DL-alanyl)-poly(L-lysine), this compound activates macrophages in vitro and becomes at least as effective as MDP. It has also been shown in other studies that after conjugation MDP(DD) remained devoid of antigenicity and of adjuvant activity although such a conjugate could increase resistance to infection. It, therefore, appears that there exists no correlation between the structure required for adjuvant activity and the structure required for macrophage activation or for enhancement of nonspecific immunity.

摘要

先前已有报道称,N-乙酰基-胞壁酰-L-丙氨酰-D-异谷氨酰胺(MDP)代表了在弗氏完全佐剂中可替代分枝杆菌的最小结构,它能在体外和体内激活巨噬细胞。在本研究中我们发现,与MDP不同,非佐剂性MDP(DD)立体异构体对巯基乙酸盐诱导的巨噬细胞的细胞抑制活性没有影响,这一活性通过[³H]胸腺嘧啶核苷摄取来测定。然而,令人惊讶的是,在与惰性载体多聚(DL-丙氨酰)-聚(L-赖氨酸)偶联后,该化合物在体外激活巨噬细胞,且至少与MDP一样有效。其他研究还表明,偶联后的MDP(DD)仍然没有抗原性和佐剂活性,尽管这样的偶联物可以增强抗感染能力。因此,佐剂活性所需的结构与巨噬细胞激活或非特异性免疫增强所需的结构之间似乎没有相关性。

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