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A Study on Immunotoxicity in Animal Models for Metal Lung

Research Project

Project/Area Number 07670399
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Hygiene
Research InstitutionFukui Medical University

Principal Investigator

KUSAKA Yukinori  Department of Environmental Health, School of Medicine, Fukui Medical University, Professor and Chairman, 医学部, 教授 (70135680)

Co-Investigator(Kenkyū-buntansha) MORITA Akemi  Fukui Medical University, Assistant Professor, 医学部, 助手 (40262638)
NAKAKUKI Kazuya  Fukui Medical University, Professor, 医学部, 教授 (90024629)
佐藤 一博  福井医科大学, 医学部, 助手 (40262620)
Project Period (FY) 1995 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1997: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1996: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1995: ¥800,000 (Direct Cost: ¥800,000)
KeywordsCobalt / Nickel / Toxicity / Lung / Allergy / Hypersensitivity / Asthma / Interstitial Pneumonitis / Immunology / Toxicology / 感作 / 免疫 / 毒性 / アレルギー
Research Abstract

The present study was aimed at clarifying mechanism for hypersensitivity lung disease caused by nickel and cobalt by using animal models. Firstly, the rat model for interstitial pneumonitis was developed with intratracheal instillation of ultrafine nickel or cobalt particles. The model with nickel presented with lasting and severe alveolitis and interstitial pneumonitis to more extent than quartz or ultrafine titanium dioxide. Moreover, the nickel model showed lymphocyte infiltrations at the advance stage. Stockiness such as tumor necrosis factor and reactive oxygen species including nitric oxide and super oxide were revealed to play roles in the persistent inflammation in the both nickel and cobalt lung models. At the same time, a guinea pig model sensitized with skin exposure to cobalt was developed. It was shown that alveolar macrophages enhanced in vitro proliferation of lymphocytes from autologous thoracic lymphnodes. Thus the result suggested a possibility that skin sensitized guinea pig model may lead to pulmonary hypersensitivity model on respiratory exposure to cobalt. Taken together, the rat model and guinea pig model made with exposure to metals were suggested to provide further knowledge on mechanism underlying nickel lung and cobalt lung disease.

Report

(4 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • 1995 Annual Research Report
  • Research Products

    (32 results)

All Other

All Publications (32 results)

  • [Publications] Kumagai, S.: "Log-normality of occupational exposure distribution." Ann Occup Hyg. 41(3). 281-286 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] KusakaY.: "Epidemiology of hard metal asthma." Occup Environ Med (formerly,Br J Ind Med). 53. 188-193 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kusaka Y.: "Decreased ventilatory function in hard metal workers." Occup Environ Med(formerly,Br J Ind Med). 53. 194-199 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Zhang Q.: "Dynamic changes of constituents in bronshoalveolar lavage fluid in experimental silicotic rats." Ind Health.34. 379-388 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kumagai S.: "Fitness of occupational exposure data to inverse Gaussian distribution." Environmental Modeling Assessment.1. 277-280 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Zhang Q.: "Differences in the extent of inflammation caused by intratracheal exposure to 3 ultrafine metals:role of free radicals." J Toxicol Environ Health. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] L.W.Chang: "Toxicology of metals." CRC Press, (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] P.Collery: "Metal Ions in Biology and Medicine.Vol.4." John Libbey Eurotext, (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kumagai S.: "Log-normality of occupational exposure distribution" Ann Occup Hyg. 41 (3). 281-286 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kusaka Y.: "Epidemiology of hard metal asthma." Occup Environ Med (formerly, Br J Ind Med). 53. 188-193 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kusaka Y.: "Decreased ventilatory function in hard metal workers." Occup Environ Med (formerly, Br J Ind Med). 53. 188-193 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Zhang Q.: "Dynamic changes of constituents in bronchoalveolar lavage fluid in experimental silicotic rats." Ind Health.34. 379-388 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kumagai S.: "Fitness of occupational exposure data to inverse Gaussian distribution." Environmental Modeling Assessment. 1. 277-280 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Zhang Q.: "Differences in the extent of inflammation caused by intratracheal exposure to 3 ultrafine metals : role of free radicals." J Toxicol Environ Health. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kusaka Y.: "Cobalt and nickel induced hard metal asthma." Toxicology of metals. CRC Press.461-468 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kusaka Y.: "Which is more immunotoxic to the respiratory system, ionic or metallic cobalt? ." Metal Ions in Biology and Medicine. Vol.4.John Libbey Eurotext. 611-613 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 森田明美: "重金属 第2回コバルトとその化合物." 日本産業衛生学会誌.39(2). A39-A40 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kusaka,Y: "Association of natural killer cell activity with serum IgE." Int Arch Allergy Immunol.112. 331-335 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kumagai,S.: "Fitness of occupational exposure data to inverse Gaussian distribution." Environmental Modeling Assessment.1. 277-280 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kumagai,S.: "Log-Normality of distribution of occupational exosure concentrations to cobalt." British Occupational Hygiene Socity.41(3). 281-286 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Zhang,Q.: "Differences in the extent of inflammtion caused by intracheal exposure to 3 ultrafine metals : role of free radicals." Journal of toxicology and Environmental Health.(in press).

    • Related Report
      1997 Annual Research Report
  • [Publications] Kusaka,Y. et al.: "Which is more immunotoxic to the respiratory system,ionic or metallic cobalt ?" Metal Ions in Biology and Medicine. VOL.4. 611-613 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kusaka,Y. et al.: "Epidemiological study of hard metal asthma." Occup Environ Med. VOL.53. 188-193 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kusaka,Y.: "Decreased ventilatory function in hard metal workers." Occup Environ Med. 53. 194-199 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Zhang,Q.,Kusaka,Y.,et al.: "Dynamic changes of constituents in bronchoalveolar lavage fluid in experimental silicotic rats" Industrial Health. 34. 379-388 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 日下幸則: "後藤 稠(編)最新医学大辞典 第2版:呼吸の項目(No.063)" 医歯薬出版, 2333 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kusaka,Y.: "Toxicology of Metals" CRC PRESS, 1198 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kusaka Y.: "Direct effect of cadmium uptake by isolated rat renal brush border membrane vesicles." Toxicol Letters. 80. 161-165 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Kusaka Y.: "Selenium status and skeletal tissue metabolism in young infants." Eur J Pediatr. (in press). (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Kusaka Y.: "Cobalt exposure level and variability in hard metal industry of Japan." Am J Ind Hyg J. (accepted). (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Kusaka Y.: "Investigation of the association between mercury sensitization and HLA-DR6." Contact Derm. (accepted). (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 日下幸則: "水銀感作に関連する要因についての疫学的研究" アレルギー. 44. 86-92 (1995)

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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