Oda T, Morinaga T, Maeda H
Proc Soc Exp Biol Med. 1986 Jan;181(1):9-17. doi: 10.3181/00379727-181-42218.
Lipophilic anionic copolymer (styrene-maleic acid; SMA) conjugates of albumin and antitumor protein neocarzinostatin (NCS) (smancs) were found to stimulate the release of H2O2 and O-2 from the peritoneal macrophages obtained from mice which had been pretreated with the heat-killed preparation of Streptococcus pyogenes (OK-432) in vivo. Some alkyl esters of SMA exhibited effects similar to protein-polymer conjugates. Among them, butyl-SMA was the most effective followed by ethyl-SMA, whereas hydrolyzed SMA showed no effect. This activity was dose-dependent but exhibited a bell-shape profile. These results suggest that the aliphatic ester residue in SMA as well as the main chain of the copolymer may be important for the activation of macrophages. A strong antitumor effect of smancs reported elsewhere may be attributed partly to the activation of macrophages in addition to the direct damage to the cellular DNA by the NCS component. A preliminary investigation of the subcellular mechanism of macrophage activation was carried out in view of membrane fluidity by the fluorescence polarization method. The results showed that the apparent decrease in the cell membrane fluidity and the degree of macrophage activation paralleled the same dose range and at similar time courses. This indicated the interaction of SMA component and macrophage cell membrane.
已发现亲脂性阴离子共聚物（苯乙烯-马来酸；SMA）与白蛋白和抗肿瘤蛋白新制癌菌素（NCS）的缀合物（smancs）可刺激从小鼠腹膜巨噬细胞释放H2O2和O-2，这些小鼠在体内已用热灭活的化脓性链球菌制剂（OK-432）进行过预处理。SMA的一些烷基酯表现出与蛋白质-聚合物缀合物相似的作用。其中，丁基-SMA最有效，其次是乙基-SMA，而水解的SMA则无作用。这种活性呈剂量依赖性，但呈现钟形曲线。这些结果表明，SMA中的脂肪族酯残基以及共聚物的主链可能对巨噬细胞的激活很重要。其他地方报道的smancs的强大抗肿瘤作用，除了NCS成分对细胞DNA的直接损伤外，可能部分归因于巨噬细胞的激活。鉴于膜流动性，通过荧光偏振法对巨噬细胞激活的亚细胞机制进行了初步研究。结果表明，细胞膜流动性的明显降低和巨噬细胞激活程度在相同剂量范围内且在相似时间进程中平行。这表明SMA成分与巨噬细胞膜之间存在相互作用。
