1998 Fiscal Year Final Research Report Summary
Free radical producing activity and intracellular signal transduction mechanisms of phagocytes by heavy metals
| Project/Area Number |
08457114
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hygiene
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| Research Institution | Kanazawa University |
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Principal Investigator |
OGINO Keiki Kanazawa University, School of Medicine, Faculty of Medicine, Professor, 医学部, 教授 (70204104)
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| Co-Investigator(Kenkyū-buntansha) |
NAGASE Hirohumi Kanazawa University, School of Medicine, Faculty of Medicine, Lecturer, 医学部, 講師 (00251918)
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| Project Period (FY) |
1996 – 1998
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| Keywords | Free radicals / Zinc oxide / Phagocytes / Intracelluar signal transduction pathway / Monoamine oxidase / Glutathione / Nitric oxide synthase / peroxynitrite |
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| Research Abstract |
The activation mechanisms of intraperitoneal-eluted rat neutrophils and mouse macrophage -like cell line Raw 264.7 by zinc oxide (ZnO) was investigated to explore the etiological mechanisms of metal fume fever induced by ZnO.The activation of phagocytes by ZnO was enhanced by the addition of glutathione (GSH) and thiol compounds. Superoxide (O2^-) and hydrogen peroxide (H2O2) may be produced by NADPH oxidase via the intracellular signal transduction pathway such as GTP-binding protein, protein kinase C, tyrosine kinase, and intracellar calcium and membraneous CR3 if ZnO was added as a stimulant to neutrophils. If GSH was added to ZnO, the production of acitive oxygen species was dependent on FcgammaR in addition to CR3. The differnce in the activation of neutrophils by ZnO and ZnO plus GSH was investigated. The activation of neutrophils by ZnO may be dependent on the production of O2^- and peoxynitrite (ONOO^-) via NADPH oxidase and nitric oxide synthase (NOS). The activation of neutrophils by ZnO plus GSH may participated in the elevated H2O2 via the activation of monoamine oxidase (MAO) mainly localized in mitochodrium. These results suggest pot only the new evidence of the origin of H2O2 associated with the activation of nuclear transcription factor and the etiology of apoptosis but also the discovery of the relationship between MAO and intracellar signal transduction mechanisms. Moreover, from the results of Raw 246.7, GSH promoted the cleaning of ZnO particles by phagocytosis.
From this research project, it is speculated that zinc fume fever may be caused by the intrinsic factor GSH in addition to ZnO particles.
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