MACROPHAGE VARIANTS IN OXYGEN-METABOLISM
MACROPHAGE VARIANTS IN OXYGEN-METABOLISM
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DOI：
10.1084/jem.152.4.808
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发表时间：
1980-01-01
影响因子：
15.3
通讯作者：
BLOOM, BR
中科院分区：
文献类型：
--
作者：
DAMIANI, G;KIYOTAKI, C;BLOOM, BR
尽管正常人的吞噬细胞具有杀死摄入的细菌和寄生虫的能力，但已知患有几种罕见遗传缺陷病的患者的吞噬细胞在杀菌活性方面存在缺陷。对这些患者的中性粒细胞的研究揭示了其还原分子氧并将其代谢为超氧阴离子、H2 O2和氧自由基的能力的根本缺陷。一个连续的小鼠巨噬细胞样细胞系，J774.16，激活己糖单磷酸分流，并产生超氧阴离子和H2 O2在适当的刺激的克隆描述。使用氮蓝四唑选择O2代谢缺陷的变体，以选择能够被佛波醇肉豆蔻酸酯乙酸酯刺激的细胞，以将染料还原为对细胞有毒的聚合物甲瓒。这些亚克隆中有四个缺乏产生超氧阴离子的能力，如通过细胞色素c还原所测量的;产生过氧化氢，如通过与细胞色素c过氧化物酶形成复合物I的能力所测量的;以及被刺激通过己糖单磷酸分流来氧化葡萄糖。这些变体似乎代表了用于研究巨噬细胞杀细胞活性的分子基础的有用模型。
Whereas phagocytic cells from normal individuals have the capacity to kill ingested bacteria and parasites, those from patients with several uncommon genetic deficiency diseases are known to be defective in bactericidal activity. Studies on neutrophils of these patients have revealed fundamental defects in their ability to reduce molecular oxygen and metabolize it to superoxide anion, H2O2, and oxygen radicals. A clone of a continuous murine macrophage-like cell line, J774.16, activates the hexose monophosphate shunt and produces superoxide anion and H2O2 on appropriate stimulation is described. Variants defective in O2 metabolism were selected using nitroblue tetrazolium to select against cells capable of being stimulated by phorbol myristate acetate to reduce the dye to the polymer formazan, which is toxic for cells. Four of these subclones were lacking in the ability to generate superoxide anion, as measured by cytochrome c reduction; to produce H2O2, as measured by the ability to form complex I with cytochrome c peroxidase; and to be stimulated to oxidize glucose via the hexose monophosphate shunt. These variants appear to represent a useful model for studying the molecular basis for macrophage cytocidal activity.