Takenawa T, Ishitoya J, Homma Y, Kato M, Nagai Y
Biochem Pharmacol. 1985 Jun 1;34(11):1931-5. doi: 10.1016/0006-2952(85)90311-9.
When guinea pig neutrophils were stimulated with chemotactic peptide [formylmethionyl-leucyl-phenylalanine (fMLP)], a marked release of lysosomal enzyme and production of superoxide anion were detected. The breakdown of phosphatidylinositol 4,5-bisphosphate (TPI) and the subsequent formation of diacylglycerol, phosphatidic acid and free arachidonic acid also occurred during the processes. Ca2+ ionophore A23187 caused an evident secretion of lysosomal enzyme but no superoxide anion production. Ca2+ ionophore also caused TPI breakdown to diacylglycerol although this breakdown was not as significant as that detected by fMLP. The tumor promotor tetradecanoylphorbol acetate (TPA), which is a strong activator of superoxide anion production but not a good stimulator of lysosomal enzyme secretion, did not cause a significant decrease of TPI or arachidonic acid release. Since TPA is known not to increase the intracellular Ca2+ level, these results suggest that lysosomal enzyme secretion is correlated closely with enhanced inositol phospholipid metabolism and Ca2+-dependent processes. On the other hand, superoxide anion production seemed to be caused mainly by Ca2+-independent processes, perhaps by protein kinase-C activation through newly formed diacylglycerol, when neutrophils were activated by chemotactic peptide.
当用趋化肽[甲酰甲硫氨酰-亮氨酰-苯丙氨酸(fMLP)]刺激豚鼠中性粒细胞时,可检测到溶酶体酶的显著释放和超氧阴离子的产生。在这些过程中还发生了磷脂酰肌醇4,5-二磷酸(TPI)的分解以及随后二酰基甘油、磷脂酸和游离花生四烯酸的形成。钙离子载体A23187导致溶酶体酶明显分泌,但不产生超氧阴离子。钙离子载体也导致TPI分解为二酰基甘油,尽管这种分解不如fMLP检测到的那样显著。肿瘤促进剂十四酰佛波醇乙酸酯(TPA)是超氧阴离子产生的强激活剂,但不是溶酶体酶分泌的良好刺激剂,它不会导致TPI或花生四烯酸释放的显著减少。由于已知TPA不会增加细胞内钙离子水平,这些结果表明溶酶体酶分泌与肌醇磷脂代谢增强和钙离子依赖过程密切相关。另一方面,当趋化肽激活中性粒细胞时,超氧阴离子的产生似乎主要由钙离子非依赖过程引起,可能是通过新形成的二酰基甘油激活蛋白激酶-C。