Eick Sigrun, Pfister Wolfgang, Stürzebecher Uta, Jarema Sigrid, Stürzebecher Jörg
Department of Oral Microbiology and Institute of Vascular Biology and Medicine, University Hospital of Jena, Germany.
Acta Biochim Pol. 2003;50(3):725-34.
Synthetic inhibitors of benzamidine type have been found to have inhibiting effects on arginine specific cysteine proteinases of P. gingivalis. The purpose of our study was to assess the effects of these inhibitors on the virulence properties of two P. gingivalis strains, the reference strain ATCC 33277 and JH16-1, a clinical isolate obtained from a patient with severe periodontitis. The inhibitors tested were pentamidine, benzamidine, three bis-benzamidine derivatives with a pentamidine-related structure, one bis-benzamidine derivative with another structure, and one arginine derivative as a negative control, each in the concentrations of 2 microM and 20 microM. As virulence criteria the following parameters were determined: arginine-specific amidolytic activity, growth inhibition, hemagglutination of sheep erythrocytes, adherence to KB cells and immuno-phagocytosis including intracellular killing. Pentamidine and the bis-benzamidine derivatives with pentamidine-related structure showed the most remarkable effects on reduction of amidolytic activity by 35%, growth inhibition and reduced hemagglutination. Except for the arginine derivative all other inhibitors tested enhanced the phagocytosis capacities of granulocytes. No clear influence of the inhibitors on adherence of P. gingivalis to KB cells was seen. Although in vitro effects of the synthetic inhibitors of cysteine proteinases on virulence of P. gingivalis were observed further in vitro tests concerning immunomodulatory effects should be done before these substances are used for therapy in clinically controlled studies.
已发现苯甲脒类合成抑制剂对牙龈卟啉单胞菌的精氨酸特异性半胱氨酸蛋白酶具有抑制作用。我们研究的目的是评估这些抑制剂对两株牙龈卟啉单胞菌毒力特性的影响，这两株菌分别是参考菌株ATCC 33277和JH16 - 1（从一名重度牙周炎患者分离得到的临床菌株）。所测试的抑制剂有喷他脒、苯甲脒、三种具有与喷他脒相关结构的双苯甲脒衍生物、一种具有另一种结构的双苯甲脒衍生物以及一种精氨酸衍生物作为阴性对照，每种抑制剂的浓度均为2微摩尔和20微摩尔。作为毒力标准，测定了以下参数：精氨酸特异性酰胺水解活性、生长抑制、绵羊红细胞的血凝作用、对KB细胞的黏附以及免疫吞噬作用（包括细胞内杀伤）。喷他脒和具有与喷他脒相关结构的双苯甲脒衍生物对酰胺水解活性降低35%、生长抑制和血凝作用减弱表现出最显著的效果。除精氨酸衍生物外，所有其他测试的抑制剂均增强了粒细胞的吞噬能力。未观察到抑制剂对牙龈卟啉单胞菌黏附KB细胞有明显影响。尽管观察到了半胱氨酸蛋白酶合成抑制剂对牙龈卟啉单胞菌毒力的体外作用，但在这些物质用于临床对照研究的治疗之前，应进一步进行有关免疫调节作用的体外试验。
