Macrophage activation by bacterial cell walls and related synthetic compounds
Macrophage activation by bacterial cell walls and related synthetic compounds
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细菌细胞壁和相关合成化合物激活巨噬细胞
作者：
H. Takada;M. Tsujimoto;K. Katō;S. Kotani;S. Kusumoto;M. Inage;T. Shiba;I. Yano;S. Kawata;K. Yokogawa
在刺激[14 C]葡糖胺掺入方面，研究了各种细菌细胞壁、M-1内切-N-乙酰胞壁酶酶消化的细菌细胞壁和合成胞壁酰二肽对豚鼠腹腔巨噬细胞的激活。所有试验细菌细胞壁制剂均显著增加巨噬细胞对[14 C]葡糖胺的摄取。一些水溶性M-1酶抑制剂也对巨噬细胞产生刺激作用，尽管发现这些酶抑制剂的活性比原始细胞壁的活性弱。此外，具有澄清剂活性的合成MurNAc-L-Ala-D-iso-Gln（MDP）显示出弱但显著的活性，而无澄清剂活性的类似物MurNAc-L-Ala-L-iso-Gln没有显示出显著的活性，至少在100微克的剂量下。对MDP的6-O-酰基衍生物的其他研究表明，6-O-（2-十四烷基十六酰基）-MDP和6-O-（3-羟基-2-十四烷基-十八酰基）-MDP表现出比MDP更强的巨噬细胞刺激作用。从上述结果可以得出结论，MDP是负责刺激豚鼠腹腔巨噬细胞细胞的细胞壁活性的基本结构，但它需要一种颗粒状态，这是由亲脂性的加和特性产生的，以充分有效地发挥活性。
Activation of peritoneal macrophages from guinea pigs by various bacterial cell walls, M-1 endo-N-acetylmuramidase enzymatically digested bacterial cell walls and synthetic muramyl dipeptides was studied in terms of stimulation of [14C] glucosamine incorporation. All test bacterial cell wall preparations significantly increased a [14C]glucosamine uptake by the macrophages. Some of the water-soluble M-1 enzyme digests also exerted stimulating effects on macrophages, although the activity of the digests was found to be weaker than those of original cell walls. Furthermore, an adjuvant-active synthetic MurNAc-L-Ala-D-isoGln (MDP) showed a weak but significant activity, whereas an adjuvant-inactive analog, MurNAc-L-Ala-L-iso-Gln, did not show a significant activity, at least with the dose of 100 microgram. Additional studies with 6-O-acyl derivatives of MDP revealed that 6-O-(2-tetradecylhexadecanoyl)-MDP and 6-O-(3-hydroxy-2-tetradecyl-octadecanoyl)-MDP exhibit stronger macrophage-stimulating effects than MDP. It can be concluded from the above findings that MDP is the essential structure responsible for stimulating the activity of cell walls on guinea pig peritoneal macrophages, but it requires a particle state, which results from an additive character of lipophilicity, to exert the activity fully and effectively.