Kroegel C, Giembycz M A, Matthys H, Westwick J, Barnes P J
Department of Thoracic Medicine, National Heart and Lung Institute, Brompton Hospital, London, United Kingdom.
Am J Respir Cell Mol Biol. 1994 Nov;11(5):593-9. doi: 10.1165/ajrcmb.11.5.7946388.
To determine the role of protein kinase C (PKC) in the signal transduction in eosinophil pathways, we have assessed the effects of the phorbol ester phorbol 12-acetate 13-myristate (PMA) on guinea pig peritoneal eosinophils challenged with platelet-activating factor (PAF). Pretreatment with PMA completely inhibited the PAF-induced release of eosinophil peroxidase (EPO) and superoxide anions and the rise in intracellular Ca2+ concentration ([Ca2+]i), with IC50s of 2 to 10 nM. This inhibition was reversed when the cells were preincubated with the PKC inhibitor staurosporine for 5 min before the addition of PMA. Staurosporine also inhibited PAF-induced EPO release but not the rise in [Ca2+]i. The inactive ester 4 alpha-phorbol 12,13-didecanoate had no inhibitory effect on eosinophil activation. Finally, PMA inhibited the binding of the PAF antagonist [3H]WEB 2086 to intact eosinophils. Taken together, these data suggest that PKC may have a physiologic role in regulating PAF-induced eosinophil responses through expression of PAF receptors on the cell surface.
为了确定蛋白激酶C（PKC）在嗜酸性粒细胞信号转导途径中的作用，我们评估了佛波酯佛波醇12 - 乙酸酯13 - 肉豆蔻酸酯（PMA）对用血小板活化因子（PAF）刺激的豚鼠腹腔嗜酸性粒细胞的影响。用PMA预处理可完全抑制PAF诱导的嗜酸性粒细胞过氧化物酶（EPO）和超氧阴离子的释放以及细胞内Ca2 +浓度（[Ca2 +]i）的升高，IC50为2至10 nM。当在加入PMA之前将细胞与PKC抑制剂星形孢菌素预孵育5分钟时，这种抑制作用被逆转。星形孢菌素也抑制PAF诱导的EPO释放，但不抑制[Ca2 +]i的升高。无活性酯4α - 佛波醇12,13 - 二十二烷酸酯对嗜酸性粒细胞活化没有抑制作用。最后，PMA抑制PAF拮抗剂[3H]WEB 2086与完整嗜酸性粒细胞的结合。综上所述，这些数据表明PKC可能通过在细胞表面表达PAF受体来调节PAF诱导的嗜酸性粒细胞反应中发挥生理作用。
