Production of Cytokines After Stimulation of Bacterial Components And Protective Role of the Cytokines to Bacterial Infection

1. 细菌脂多糖（LPS）激活巨噬细胞的机制当LPS刺激小鼠腹腔巨噬细胞时，巨噬细胞产生多种细胞因子，增强其杀菌能力。我们研究了LPS刺激后巨噬细胞的生化事件。钙调素系统与LPS激活巨噬细胞产生IL-1有关，而蛋白激酶C和环AMP以及环GMP似乎与之无关。lps刺激后，巨噬细胞细胞膜和胞浆内部分蛋白发生磷酸化。我们纯化了胞浆中最显性的磷酸化蛋白pp65，发现pp65是丝氨酸激酶的底物，其结构与人的塑蛋白相似。细胞因子在细菌感染中的保护作用。将重组细胞因子（ifn - γ、tnf - α和β、IL-1、IL-6或G-CSF）注射到小鼠体内，增强了小鼠对鼠伤寒沙门氏菌（或肠炎沙门氏菌）和铜绿假单胞菌的杀菌能力和保护能力。部分细胞因子或细胞因子联合LPS治疗效果更好。这种增强部分是由于吞噬细胞的招募和单个细胞的吞噬和杀伤能力的增加。

1. Mechanisms of macrophage activation by bacterial lipopolysaccharide (LPS). When murine peritoneal macrophages are stimulated by LPS, the macrophages produce various kinds of cytokines, and augment their bactericidal capacity. We investigated biochemical events in the macrophages after the stimulation of LPS. Calmodulin system was relevant to the macrophage activation by LPS to produce IL-1, while protein-kinase C and cyclic AMP as well as cyclic GMP seemed to be irrelevant to it. Shortly after LPS-stimulation, some proteins in the cell membrane and cytosol of the macrophages were phosphorylated. We purified the most dominant phosphorylated protein (pp65) in the cytosol, and found that the pp 65 was a substrate of serine kinase with a structure similar to human plastin.2. Protective role of cytokines in the bacterial infection. When some of recombinant cytokines (either IFN-gamma, TNF-alpha and beta, IL-1, IL-6, or G-CSF) was injected into mice, bactericidal capacity and protectivity in the mice against Salmonella typhimurium (or S. enteritidis) and Pseudomonas aeruginosa were augmented. Combination of some of the cytokines or cytokine plus LPS was more effective. The augmentaion was partly due to the recruitment of phagocytic cells and the increment of the phagocytic and killing abilities of individual cells.