Klassen D K, Conkling P R, Sagone A L
Infect Immun. 1982 Mar;35(3):818-25. doi: 10.1128/iai.35.3.818-825.1982.
We have characterized the effects of phorbol myristate acetate (PMA) on human monocyte and neutrophil oxidative metabolism and antibody-dependent cytotoxicity toward anti-D sensitized human erythrocytes (RBC) and a human lymphoblastoid cell line (CEM). Hexose monophosphate shunt activity was measured by [1-(14)C]glucose oxidation and target lysis by (51)Cr release. PMA produced a dose-dependent stimulation of hexose monophosphate shunt activity. Neutrophils responded with higher hexose monophosphate shunt activity and at a lower PMA concentration than did monocytes. PMA increased monocyte lysis of antibody-sensitized RBC by two-thirds, but did not affect lysis of CEM targets. Neutrophils were unable to lyse either antibody-sensitized or nonsensitized RBC without the addition of PMA. When PMA was added, lysis of both targets increased markedly. Neutrophils without PMA were able to lyse a small number of both antibody-sensitized and nonsensitized CEM targets. PMA also increased neutrophil lysis of these targets. Target lysis by neutrophils from a patient with chronic granulomatous disease, cells unable to produce reactive oxygen species, was not increased by PMA. Chronic granulomatous disease monocytes, however, responded to PMA by more than doubling lysis of antibody-sensitized RBC. Hypoxia inhibited PMA augmentation of antibody-sensitized RBC lysis by neutrophils, but not by monocytes. Generation of reactive oxygen species by the xanthine-xanthine oxidase system inhibited CEM growth, but did not cause lysis, indicating that in some cases oxidative injury may be nonlytic. We suggest that PMA augments neutrophil cytotoxicity to tumor and RBC targets by stimulating reactive oxygen species-mediated lysis, but in monocytes augmentation of lysis is due to activation of a nonoxidative mechanism of lysis.
我们已对佛波醇肉豆蔻酸酯乙酸酯（PMA）对人单核细胞和中性粒细胞氧化代谢以及对抗-D致敏的人红细胞（RBC）和人淋巴母细胞系（CEM）的抗体依赖性细胞毒性的影响进行了表征。通过[1-(14)C]葡萄糖氧化测量磷酸己糖旁路活性，并通过(51)Cr释放测量靶细胞裂解。PMA产生了剂量依赖性的磷酸己糖旁路活性刺激。中性粒细胞比单核细胞对PMA的反应更强，磷酸己糖旁路活性更高，且所需PMA浓度更低。PMA使单核细胞对抗体致敏的RBC的裂解增加了三分之二，但不影响对CEM靶细胞的裂解。在不添加PMA的情况下，中性粒细胞无法裂解抗体致敏或未致敏的RBC。添加PMA后，两种靶细胞的裂解均显著增加。未添加PMA的中性粒细胞能够裂解少量抗体致敏和未致敏的CEM靶细胞。PMA也增加了中性粒细胞对这些靶细胞的裂解。来自慢性肉芽肿病患者的中性粒细胞（无法产生活性氧的细胞）对PMA的反应未增加靶细胞裂解。然而，慢性肉芽肿病单核细胞对PMA的反应是使抗体致敏的RBC裂解增加了一倍多。缺氧抑制了PMA增强中性粒细胞对抗体致敏的RBC的裂解作用，但不影响单核细胞。黄嘌呤-黄嘌呤氧化酶系统产生活性氧抑制了CEM的生长，但未导致裂解，这表明在某些情况下氧化损伤可能是非裂解性的。我们认为，PMA通过刺激活性氧介导的裂解增强中性粒细胞对肿瘤和RBC靶细胞的细胞毒性，但在单核细胞中，裂解的增强是由于非氧化裂解机制的激活。
