Mordmüller B, Turrini F, Long H, Kremsner P G, Arese P
Sektion Humanparasitologie, Institut für Tropenmedizin, Universität Tübingen, Germany.
Eur Cytokine Netw. 1998 Sep;9(3):239-45.
Glucose 6-phosphate dehydrogenase (G6PD) activity and oxidative burst were measured in neutrophils and monocytes from five, hemizygous, G6PD-deficient (Mediterranean variant) individuals and five normal controls. Additionally, tumor necrosis factor (TNF), interleukin-10 (IL-10), interleukin-12 (IL-12) release and phagocytosis of the malarial pigment hemozoin or opsonized erythrocytes (RBC) were measured in monocytes recovered from G6PD-deficient and normal individuals. G6PD activity was significantly lower in "deficient monocytes" (38% residual activity, p = 0.01) and not significantly different in "deficient neutrophils" (79% residual activity, p = 0.83) compared to homologous leukocytes recovered from normal controls. Oxidative burst was not significantly different in "deficient" versus "normal" neutrophils and monocytes. Previous phagocytosis of hemozoin decreased the phorbol ester induced oxidative burst in "deficient" and "normal" monocytes but not in neutrophils. Phagocytosis of hemozoin and RBC strongly stimulated cytokine production. With the exception of IL-10, the cytokine production pattern was comparable in "deficient" versus "normal" cells. Incubation with high concentrations of hemozoin (equivalent to 300 RBC per monocyte) strongly stimulated TNF production. Lipopolysaccharide (LPS) had an additive effect on TNF production induced by hemozoin or opsonized RBC. IL-12 production was induced only by the presence of large amounts of hemozoin. IL-10 production was increased in normal monocytes incubated with RBC or hemozoin. LPS increased IL-10 production significantly in monocytes incubated with RBC or low amounts of hemozoin (equivalent to 30 RBC per monocyte), but had no effect when given alone or in conjunction with high concentrations of hemozoin. Interestingly, deficient monocytes produced less IL-10 than normal cells under these conditions. In conclusion, except for IL-10 production, we did not find major functional differences between neutrophils and monocytes from individuals with or without the Mediterranean G6PD mutation.
对5名半合子葡萄糖-6-磷酸脱氢酶（G6PD）缺乏（地中海型变异）个体和5名正常对照者的中性粒细胞和单核细胞进行了G6PD活性和氧化爆发检测。此外，还检测了从G6PD缺乏个体和正常个体中分离出的单核细胞中肿瘤坏死因子（TNF）、白细胞介素-10（IL-10）、白细胞介素-12（IL-12）的释放以及疟色素疟原虫血色素或调理红细胞（RBC）的吞噬作用。与从正常对照者中分离出的同源白细胞相比，“缺乏的单核细胞”中的G6PD活性显著降低（残余活性为38%，p = 0.01），而“缺乏的中性粒细胞”中的G6PD活性无显著差异（残余活性为79%，p = 0.83）。“缺乏的”与“正常的”中性粒细胞和单核细胞的氧化爆发无显著差异。先前对疟原虫血色素的吞噬作用降低了佛波酯诱导的“缺乏的”和“正常的”单核细胞中的氧化爆发，但对中性粒细胞无此作用。疟原虫血色素和RBC的吞噬作用强烈刺激细胞因子的产生。除IL-10外，“缺乏的”与“正常的”细胞中的细胞因子产生模式具有可比性。用高浓度的疟原虫血色素（相当于每个单核细胞300个RBC）孵育强烈刺激TNF的产生。脂多糖（LPS）对疟原虫血色素或调理RBC诱导的TNF产生具有相加作用。仅在存在大量疟原虫血色素时才诱导IL-12的产生。用RBC或疟原虫血色素孵育正常单核细胞时，IL-10的产生增加。LPS在与RBC或少量疟原虫血色素（相当于每个单核细胞30个RBC）孵育的单核细胞中显著增加IL-10的产生，但单独给予或与高浓度疟原虫血色素联合给予时无作用。有趣的是，在这些条件下，缺乏的单核细胞产生的IL-10比正常细胞少。总之，除IL-10的产生外，我们未发现有或无地中海G6PD突变个体的中性粒细胞和单核细胞之间存在主要功能差异。
