Dieter P, Schulze-Specking A, Fitzke E
Institute of Molecular Cell Biology, Freiberg, F.R.G.
Cell Signal. 1991;3(1):65-71. doi: 10.1016/0898-6568(91)90009-j.
This study evaluates the role of inositol phosphates as possible mediators of the activation of phospholipase A2 and NADPH oxidase in cultured rat liver macrophages. Inositol phosphate formation was achieved by zymosan, immune complexes, latex particles and calcium ionophore while the release of arachidonic acid and the formation of prostaglandin E2 was also elicited by phorbol ester and NaF, but not by latex particles; generation of superoxide was obtained by zymosan and phorbol ester only. The kinetics of the formation of inositol phosphates revealed that within the first few minutes after zymosan addition inositol trisphosphate was formed, followed by inositol bisphosphate and inositol monophosphate. Pre-treatment of the cells with dexamethasone or removal of extracellular calcium led to an inhibition of the zymosan-induced formation of inositol phosphates and prostaglandin E2 but had no effect on the generation of superoxide; inhibition of the Na+/H+ exchanger by removal of extracellular sodium ions led to a decrease of the zymosan-induced synthesis of prostaglandin E2, but did not affect the formation of inositol phosphates and superoxide. Pre-treatment of the cells with phorbol ester decreased the zymosan-induced synthesis of prostaglandin E2 and superoxide, but even enhanced the zymosan-induced formation of inositol phosphates. These data indicate that in cultured rat liver macrophages the formation of prostaglandins and superoxide cannot be correlated to an activation of phospholipase C.
本研究评估了肌醇磷酸酯作为培养的大鼠肝脏巨噬细胞中磷脂酶A2和NADPH氧化酶激活的可能介质的作用。酵母聚糖、免疫复合物、乳胶颗粒和钙离子载体可促使肌醇磷酸酯形成，而花生四烯酸的释放和前列腺素E2的形成也可由佛波酯和NaF引发，但乳胶颗粒不能；仅酵母聚糖和佛波酯可产生超氧化物。肌醇磷酸酯形成的动力学表明，在添加酵母聚糖后的最初几分钟内，肌醇三磷酸形成，随后是肌醇二磷酸和肌醇一磷酸。用地塞米松预处理细胞或去除细胞外钙可抑制酵母聚糖诱导的肌醇磷酸酯和前列腺素E2的形成，但对超氧化物的产生没有影响；去除细胞外钠离子抑制Na+/H+交换体可导致酵母聚糖诱导的前列腺素E2合成减少，但不影响肌醇磷酸酯和超氧化物的形成。用佛波酯预处理细胞可减少酵母聚糖诱导的前列腺素E2和超氧化物的合成，但甚至会增强酵母聚糖诱导的肌醇磷酸酯的形成。这些数据表明，在培养的大鼠肝脏巨噬细胞中，前列腺素和超氧化物的形成与磷脂酶C的激活无关。
