Nakajima R, Yshida Y, Akahane K, Sekiguchi M, Osada Y
Research Institute, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
Arzneimittelforschung. 1991 Jan;41(1):60-5.
Repeated subcutaneous injections of romurtide (N2-[(N-acetylmuramoyl)-L-alanyl-D-isoglutaminyl]-N6-stearoyl-L-lysine, MDP-Lys(L18), muroctasin; CAS 78113-36-7), a synthetic muramyl dipeptide derivative, increased significantly the number of peripheral neutrophils and monocytes in a dose-dependent fashion in healthy cynomolgus monkeys (Macaca fascicularis). The number of platelets was also increased significantly in monkeys with repeated dosing of romurtide. After single dosing of romurtide (1 mg/head), neutrophils counts showed a marked increase within 24 h and at 120 h after romurtide injection. Monocytes counts were decreased transiently until 8 h, but were increased persistently from 48 to 120 h after injection. Lymphocytes counts were stable throughout the experimental period except for a significant decrease until 24 h. In addition, romurtide stimulated blood neutrophils and monocytes in vivo for enhanced chemiluminescence (CL) responses to opsonized Escherichia coli. When peripheral monocytes from monkeys were incubated with various concentrations of romurtide in vitro, production of colony-stimulating factors (CSFs), interleukin-1 (IL-1) and interleukin-6 (IL-6) by the cells was enhanced significantly, indicating that the augmenting effects of romurtide on the production of various monokines including CSFs by monocytes are involved in the mechanisms of hematopoiesis and enhanced CL generation by phagocytic cells in vivo.
重复皮下注射罗莫肽(N2-[(N-乙酰基胞壁酰)-L-丙氨酰-D-异谷氨酰胺基]-N6-硬脂酰-L-赖氨酸,MDP-Lys(L18),muractasin;CAS 78113-36-7),一种合成的胞壁酰二肽衍生物,在健康食蟹猴(食蟹猕猴)中以剂量依赖的方式显著增加外周血中性粒细胞和单核细胞的数量。在重复给药罗莫肽的猴子中,血小板数量也显著增加。单次注射罗莫肽(1mg/只)后,中性粒细胞计数在注射后24小时内及120小时显著增加。单核细胞计数在8小时内短暂下降,但在注射后48至120小时持续增加。淋巴细胞计数在整个实验期间保持稳定,除了在24小时内显著下降。此外,罗莫肽在体内刺激血液中的中性粒细胞和单核细胞,增强对调理过的大肠杆菌的化学发光(CL)反应。当体外将猴子的外周单核细胞与不同浓度的罗莫肽孵育时,细胞产生集落刺激因子(CSF)、白细胞介素-1(IL-1)和白细胞介素-6(IL-6)的能力显著增强,这表明罗莫肽对单核细胞产生包括CSF在内的各种单核因子的增强作用参与了体内造血机制和吞噬细胞增强CL生成的过程。