Roos D, Weening R S, Wyss S R, Aebi H E
J Clin Invest. 1980 Jun;65(6):1515-22. doi: 10.1172/JCI109817.
To investigate the importance of catalase as a protecting enzyme against oxidative damage in phagocytic leukocytes, we have tested the functional capacity of neutrophils from two individuals homozygous for Swiss-type acatalasemia and from two individuals heterozygous for this deficiency. In the former cells, 25-30% of residual activity of catalase was present. In the latter cells, the values were close to normal. Chemotaxis towards casein, release of lysosomal enzymes and hydrogen peroxide during phagocytosis of zymosan, and intracellular killing of Staphylococcus aureus were normal in all cells tested. Inhibition of heme enzymes with azide (2 mM) enhanced the respiration and hexose monophosphate shunt activity of normal, but not of homozygous acatalasemic, neutrophils. This indicates that the enhancement in normal cells is, at least in part, due to catalase inhibition. After 15 min preincubation with an H(2)O(2)-generating system (glucose plus glucose oxidase), the respiratory response to zymosan phagocytosis was strongly depressed in the homozygous acatalasemic and in normal, azide-treated neutrophils, but not in normal, untreated cells. Under these conditions, the release of lysosomal enzymes was depressed and that of lactate dehydrogenase enhanced, in catalase-deficient and in catalase-inhibited, but not in normal, neutrophils. During prolonged incubation with the H(2)O(2)-generating system (30-60 min), the reduction level of intracellular glutathione remained high and the hexose monophosphate shunt continued to operate normally in all cells tested. Thus, although the function of neutrophils without catalase activity was depressed by extracellular hydrogen peroxide, the H(2)O(2) degradation via the glutathione redox system remained operative. The results indicate that the glutathione redox system by itself efficiently protects phagocytosing neutrophils against their own oxidative products. During heavy external oxidative stress, however, both catalase and the glutathione redox system are needed for adequate protection.
为了研究过氧化氢酶作为一种保护酶在吞噬性白细胞中抵抗氧化损伤的重要性，我们检测了两名瑞士型无过氧化氢酶血症纯合个体以及两名该缺陷杂合个体的中性粒细胞的功能能力。在前一种细胞中，存在25% - 30%的过氧化氢酶残余活性。在后一种细胞中，该值接近正常。在所有测试细胞中，对酪蛋白的趋化性、吞噬酵母聚糖过程中溶酶体酶和过氧化氢的释放以及对金黄色葡萄球菌的细胞内杀伤均正常。用叠氮化物（2 mM）抑制血红素酶可增强正常中性粒细胞的呼吸和磷酸己糖旁路活性，但对纯合无过氧化氢酶血症中性粒细胞无此作用。这表明正常细胞中的增强至少部分归因于过氧化氢酶的抑制。在用产H₂O₂系统（葡萄糖加葡萄糖氧化酶）预孵育15分钟后，纯合无过氧化氢酶血症中性粒细胞以及正常的、经叠氮化物处理的中性粒细胞对酵母聚糖吞噬的呼吸反应强烈受抑，但正常的、未处理细胞不受影响。在这些条件下，溶酶体酶的释放在过氧化氢酶缺陷和过氧化氢酶抑制的中性粒细胞中受抑，而乳酸脱氢酶的释放增强，但正常中性粒细胞不受影响。在用产H₂O₂系统长时间孵育（30 - 60分钟）期间，所有测试细胞内谷胱甘肽的还原水平保持较高，磷酸己糖旁路继续正常运作。因此，尽管无过氧化氢酶活性的中性粒细胞功能受到细胞外过氧化氢的抑制，但通过谷胱甘肽氧化还原系统的H₂O₂降解仍在起作用。结果表明，谷胱甘肽氧化还原系统自身能有效保护吞噬中的中性粒细胞免受其自身氧化产物的损伤。然而，在严重的外部氧化应激期间，过氧化氢酶和谷胱甘肽氧化还原系统都需要以提供充分的保护。
