Capsoni F, Minonzio F, Ongari A M, Bonara P, Guidi G, Zanussi C
Istituto di Medicina Interna, University of Milan, Italy.
Int J Immunopharmacol. 1991;13(2-3):227-33. doi: 10.1016/0192-0561(91)90102-d.
RU41740 is a glycoprotein extract from Klebsiella pneumoniae with immunomodulating properties under different experimental conditions. In particular the compound is able to stimulate several functions of human phagocytes in vitro and ex vivo. Using monoclonal antibodies and flow cytometry, in this work we assessed the effect of RU41740 on surface expression of receptors for C3b (CR1) and C3bi (CR3) in human phagocytic cells in vitro. The incubation of whole blood with varying RU41740 concentrations led to a dose-dependent increase in surface expression of CR1 and CR3 on both neutrophils and monocytes when compared with control samples incubated in buffer alone. The maximal drug-induced enhancement of complement receptors was: 291% +/- 13.4% for CR1 and 265% +/- 8.5% for CR3 in neutrophils; 117% +/- 4.5% for CR1 and 98% +/- 4.1% for CR3 in monocytes. These peak effects were observed using RU41740 at a final concentration of 10 micrograms/ml and were similar to those induced by optimal concentrations of the activating compound N-formyl-methionyl-leucyl-phenylalanine (10(-7)M). Polymyxin B did not modify the RU41740-induced enhancement of CR1 and CR3 expression on phagocytes, suggesting no role for endotoxin in this activity. These results define, at least in part, the mechanism of action of RU41740 on human phagocytes in vitro and could be relevant to in vivo events during RU41740 treatment.
RU41740是一种从肺炎克雷伯菌中提取的糖蛋白，在不同实验条件下具有免疫调节特性。特别是该化合物能够在体外和离体条件下刺激人类吞噬细胞的多种功能。在本研究中，我们使用单克隆抗体和流式细胞术评估了RU41740对体外人类吞噬细胞中C3b受体（CR1）和C3bi受体（CR3）表面表达的影响。与仅在缓冲液中孵育的对照样品相比，用不同浓度的RU41740孵育全血会导致中性粒细胞和单核细胞表面CR1和CR3的表达呈剂量依赖性增加。药物诱导的补体受体最大增强幅度为：中性粒细胞中CR1为291%±13.4%，CR3为265%±8.5%；单核细胞中CR1为117%±4.5%，CR3为98%±4.1%。使用终浓度为10微克/毫升的RU41740观察到了这些峰值效应，且与由最佳浓度的激活化合物N-甲酰甲硫氨酰-亮氨酰-苯丙氨酸（10⁻⁷M）诱导的效应相似。多粘菌素B并未改变RU41740诱导的吞噬细胞上CR1和CR3表达的增强，这表明内毒素在该活性中不起作用。这些结果至少部分地定义了RU41740在体外对人类吞噬细胞的作用机制，并且可能与RU41740治疗期间的体内事件相关。
