Takada H, Tsujimoto M, Kotani S, Kusumoto S, Inage M, Shiba T, Nagao S, Yano I, Kawata S, Yokogawa K
Infect Immun. 1979 Aug;25(2):645-52. doi: 10.1128/iai.25.2.645-652.1979.
Stimulation of [(3)H]thymidine incorporation of thymocytes and splenocytes from guinea pigs by various bacterial cell walls and their peptidoglycans, by enzymatic digests, and by synthetic muramyl dipeptides was studied as an indication of mitogenic activity. Cell wall and peptidoglycan preparations, isolated from 19 strains belonging to 18 different species, definitely increased [(3)H]thymidine incorporation of thymocytes as well as splenocytes, regardless of mycolic acid contents as a non-peptidoglycan component. Both the cell walls from Nocardia corynebacteriodes (containing mycolic acids) and those from Streptomyces gardneri (lacking mycolic acids) showed far stronger mitogenic activities on splenocytes than other cell walls (stimulation index, 25 to 30). Furthermore, water-soluble enzymatic digests, notably the endopeptidase digests, which generally were greater in degree of polymerization of peptidoglycan subunits than the glycosidase digests obtained from representative cell walls, were found to have as distinct a stimulating activity on splenocytes as the original cell walls. In contrast, solubilization of the cell walls by enzymes, irrespective of endopeptidases or glycosidases, was accompanied by disappearance of the mitogenic activity on thymocytes. On the other hand, studies with synthetic 6-O-acyl-MurNAc-l-Ala-d-isoGln preparations (6-O-acyl-MDPs) revealed that 6-O-stearoyl-MDP and 6-O-(2-tetradecylhexadecanoyl)-MDP, unlike MDP, had distinct mitogenic activity on thymocytes, whereas their activity on splenocytes was rather weaker than MDP itself. The findings presented here suggest that MDP is the minimal structure for the mitogenic activities of bacterial cell walls on guinea pig splenocytes, but that MDP, though distinctively active by itself, requires a polymerized form to exert effectively its inherent stimulating activities on splenocytes. On the other hand, on thymocytes, MDP, unless it takes a particular form or has appropriate additive groups, cannot exert its mitogenic activities.
研究了各种细菌细胞壁及其肽聚糖、酶消化产物和合成的胞壁酰二肽对豚鼠胸腺细胞和脾细胞掺入[³H]胸腺嘧啶核苷的刺激作用，以此作为有丝分裂原活性的指标。从18个不同物种的19个菌株中分离得到的细胞壁和肽聚糖制剂，无论作为非肽聚糖成分的分枝菌酸含量如何，均能显著增加胸腺细胞和脾细胞的[³H]胸腺嘧啶核苷掺入量。棒状诺卡氏菌（含分枝菌酸）和加德纳链霉菌（不含分枝菌酸）的细胞壁对脾细胞的有丝分裂原活性均远强于其他细胞壁（刺激指数为25至30）。此外，发现水溶性酶消化产物，特别是内肽酶消化产物，其肽聚糖亚基的聚合度通常比从代表性细胞壁获得的糖苷酶消化产物更高，对脾细胞具有与原始细胞壁一样明显的刺激活性。相反，无论使用内肽酶还是糖苷酶，酶对细胞壁的溶解都会伴随着对胸腺细胞有丝分裂原活性的消失。另一方面，对合成的6 - O - 酰基 - MurNAc - l - Ala - d - isoGln制剂（6 - O - 酰基 - MDPs）的研究表明，与MDP不同，6 - O - 硬脂酰 - MDP和6 - O -（2 - 十四烷基十六酰基）- MDP对胸腺细胞具有明显的有丝分裂原活性，而它们对脾细胞的活性则比MDP本身弱得多。此处呈现的研究结果表明，MDP是细菌细胞壁对豚鼠脾细胞有丝分裂原活性的最小结构，但MDP虽然自身具有明显活性，却需要聚合形式才能有效地对脾细胞发挥其固有的刺激活性。另一方面，对于胸腺细胞，MDP除非以特定形式存在或具有合适的附加基团，否则无法发挥其有丝分裂原活性。
