Hiramatsu K, Rosen H, Heinecke J W, Wolfbauer G, Chait A
Arteriosclerosis. 1987 Jan-Feb;7(1):55-60. doi: 10.1161/01.atv.7.1.55.
Human mononuclear cells were used to evaluate the role of superoxide in the oxidation of low density lipoprotein (LDL). Unstimulated cells produced little superoxide or LDL oxidation as assayed by lipid peroxide content. Stimulation of the cells with phorbol myristate acetate (PMA) resulted in an increase both in superoxide production and in LDL oxidation. Mononuclear cell-mediated LDL oxidation was time- and cell number-dependent and was markedly enhanced by the presence of Fe (10 microM). Superoxide was required for the initiation of LDL oxidation as indicated by inhibition of the reaction by early addition of superoxide dismutase (SOD). Propagation of LDL oxidation was superoxide-independent, since the later addition of SOD resulted in progressively less inhibition of LDL oxidation. Propagation of LDL oxidation also was, in part, cell-independent as indicated by continued oxidation of LDL when mononuclear cells were removed following a 1 to 8 hour period with cells. Optimal LDL oxidation required the presence of mononuclear cells throughout the incubation period, suggesting that cellular factors in addition to superoxide play a role in LDL oxidation. Further evidence for the role of superoxide in the oxidation of LDL by mononuclear cells was obtained with cells from patients with genetic deficiencies of either superoxide generation (chronic granulomatous disease) or myeloperoxidase. PMA-stimulated cells from a patient with chronic granulomatous disease neither generated superoxide nor modified LDL. Incubation of LDL with cells from a patient with myeloperoxidase deficiency (in which superoxide production is normal or increased) resulted in oxidation of the lipoprotein equivalent to that observed with normal cells. Other inhibitors of oxidation reactions also were tested.(ABSTRACT TRUNCATED AT 250 WORDS)
人类单核细胞被用于评估超氧化物在低密度脂蛋白（LDL）氧化中的作用。通过脂质过氧化物含量测定，未受刺激的细胞产生的超氧化物或LDL氧化极少。用佛波酯（PMA）刺激细胞会导致超氧化物生成和LDL氧化均增加。单核细胞介导的LDL氧化具有时间和细胞数量依赖性，并且在存在铁（10微摩尔）时显著增强。如早期添加超氧化物歧化酶（SOD）抑制反应所示，LDL氧化的起始需要超氧化物。LDL氧化的传播不依赖超氧化物，因为后期添加SOD对LDL氧化的抑制作用逐渐减弱。LDL氧化的传播部分也不依赖细胞，如在细胞培养1至8小时后去除单核细胞时LDL仍持续氧化所示。最佳的LDL氧化需要在整个孵育期都存在单核细胞，这表明除超氧化物外的细胞因子在LDL氧化中起作用。通过来自超氧化物生成遗传缺陷（慢性肉芽肿病）或髓过氧化物酶遗传缺陷患者的细胞，获得了超氧化物在单核细胞介导的LDL氧化中作用的进一步证据。慢性肉芽肿病患者的PMA刺激细胞既不产生超氧化物也不修饰LDL。将LDL与髓过氧化物酶缺乏患者的细胞（其中超氧化物产生正常或增加）一起孵育，导致脂蛋白氧化，与正常细胞观察到的情况相当。还测试了其他氧化反应抑制剂。（摘要截断于250字）
