Molecular mechanisms of leukocytes activation by heavy metals : Free radical generation system

重金属激活白细胞的分子机制：自由基生成系统

• 批准号: 05454228
• 负责人: OGINO Keiki
• 金额: $ 1.15万
• 依托单位: Kanazawa University (1995)Yamaguchi University (1993-1994)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05454228/
• 关键词: Zinc fume fever; Superoxide; Neutrophil; Macrophage; Intracellular signal transduction pathway; Calcium; Protein kinase C; Tyrosine protein kinase; 細胞内情報伝達機構; グルタチオン; チロシンキナーゼ; 亜鉛; 水酸化亜鉛; 酸化亜鉛; 細胞内情報伝達; カルシウムイオン; プロティンキナーゼC; 受容体

The mechanisms of activation of alveolar macrophages and neutrophils induced by heavy metals, mainly zinc, and then metal chelator were investigated by monitoring the release of superoxide in order to resolve the pathogenesis of metal fume fever from a view point of signal transduction. The effciency of superoxide radical production by zinc compounds was ranked in order as zinc sulfate (ZnSO4) <<zinc oxide (ZnO) <zinc hydroxide (Zn(OH)2). The mechanisms of the signal transduction of three zinc compounds varied with each other. Zinc ions from zinc sulfate stimulated hydrogen peroxide. The hydrogen peroxide production was not superoxide, independent on calcium and less dependent on protein kinase C.It was suggested that the activation of neutrophils by zinc ions might be dependent on unknown signal transduction pathway. Zinc oxide stimulated neutrophils in the absence of extracellular calcium and the stimulation was enhanced by addition of GSH (a priming effect). Therefore, it was sugges … More ted that zinc oxide might stimulate superoxide production of neutrophils via receptors closely related with tyrosine protein kinase. On the other hand, zinc hydroxide stimulated neutrophils by the process of the influx of calcium from extracellular fluids and the activation of protein kinase C.The major mechanism of neutrophils activation by zinc hydroxide may be dependent on the phagocytosis. These results suggested that a subtle molecular change of zinc compounds might be contributed to the recognition of the phagocytes.Stimulation of neutrophils by zinc hydroxide reduced NO release from the same cells. This phenomenon may result from the interaction with NO and superoxide or NO and zunc hydroxide. There was no expression of LAF-1 on the surface of cell membrane with the stimulation of zinc hydroxide. A monolonal antibody to LAF-1 did not suppress the activation of neutrophils by zinc hydroxide.The activation of neutrophils by cadmium and a metal chelator of diethydithiocarbamate, and the suppression of activated phagocytes by gadolinium were also observed. Less

通过监测超氧化物的释放，研究重金属（主要是锌）和金属螯合剂诱导肺泡巨噬细胞和中性粒细胞活化的机制，以从信号转导的角度解决金属烟雾热的发病机制。锌化合物产生超氧自由基的效率排序为硫酸锌(ZnSO4)<<氧化锌(ZnO)<氢氧化锌(Zn(OH)2)。三种锌化合物的信号转导机制各不相同。硫酸锌中的锌离子刺激过氧化氢。过氧化氢的产生不是超氧化物，不依赖于钙，对蛋白激酶C的依赖性较小。提示锌离子对中性粒细胞的激活可能依赖于未知的信号转导途径。氧化锌在没有细胞外钙的情况下刺激中性粒细胞，并且通过添加谷胱甘肽（启动效应）增强刺激。因此，有人认为氧化锌可能通过与酪氨酸蛋白激酶密切相关的受体刺激中性粒细胞产生超氧化物。另一方面，氢氧化锌通过细胞外液中钙的流入和蛋白激酶C的激活过程来刺激中性粒细胞。氢氧化锌激活中性粒细胞的主要机制可能依赖于吞噬作用。这些结果表明，锌化合物的细微分子变化可能有助于吞噬细胞的识别。氢氧化锌对中性粒细胞的刺激减少了同一细胞中NO的释放。这种现象可能是由于 NO 与超氧化物或 NO 与氢氧化锌相互作用所致。氢氧化锌刺激后细胞膜表面无LAF-1表达。 LAF-1单克隆抗体不抑制氢氧化锌对中性粒细胞的活化。还观察到镉和二乙基二硫代氨基甲酸盐金属螯合剂对中性粒细胞的活化，以及钆对活化吞噬细胞的抑制。较少的

项目成果

Yukie Izumi: "Effects of dicthyldithiocarbamate on activating mcchanisms of ncutrophils." Pharmacology & Toxicology. 74. 280-286 (1994)

Yukie Izumi：“二乙基二硫代氨基甲酸酯对嗜中性粒细胞激活机制的影响。”

Yuko Takeyama, Keiki Ogino Hiroyuki Segawa, Taizo Uda and Tatsuya Houbara: "Effects of zinc on production of active oxygen species by rat neutrophils." Pharmacology & Toxicology. 76. 50-55 (1995)

Yuko Takeyama、Keiki Ogino Hiroyuki Sekawa、Taizo Uda 和 Tatsuya Hobara：“锌对大鼠中性粒细胞产生活性氧的影响。”

Yukie Izumi: "Effects diethyldithiocarbamate on activating mechanisms of neutrophils." Pharmacology & Toxicoloy.(1994)

Yukie Izumi：“影响二乙基二硫代氨基甲酸盐对中性粒细胞激活机制的影响。”

泉 由紀枝: "Diethyldithiocarbamateが好中球のsuperoxide及びnitric oxide産生に与える影響" 山口医学. 42. 379-386 (1994)

Yukie Izumi：“二乙基二硫代氨基甲酸酯对中性粒细胞中超氧化物和一氧化氮产生的影响”Yamaguchi Medical。 42. 379-386 (1994)

Toshiko Ueda, Tsuyoshi Maekawa, Daikai Sadamitu, Shuzo Oshita, Keiki Ohino and Kazuyuki Nakamura: "The determination of nitrite and nitrate in human blood plasma by capillary zone electrophoresis." Electrophoresis. 16. 1002-1004 (1995)

Toshiko Ueda、Tsuyoshi Maekawa、Daikai Sadamitu、Shuzo Oshita、Keiki Ohino 和 Kazuyuki Nakamura：“通过毛细管区带电泳测定人血浆中的亚硝酸盐和硝酸盐。”