| Project/Area Number |
02670352
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | University of Occupational and Environmental Health JAPAN |
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Principal Investigator |
KIDO MASAMITSU University of Occupational and Environmental Health JAPAN School of Medicine, Professor, 医学部, 教授 (10101172)
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| Co-Investigator(Kenkyū-buntansha) |
TANAKA Isamu University of Occupational and Environmental Health JAPAN School of Medicine, Pr, 医学部, 教授 (00038035)
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| Project Period (FY) |
1990 – 1991
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| Project Status |
Completed (Fiscal Year 1991)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1991: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1990: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | Trimellitic anhydride (TMA) / MSIS / Occupational asthme / Immune reaction / Lung injury / Airway hyperresponsiveness / Guinea pig / 低分子化合物 / 気道反応 / 免疫 / アレルギ- |
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| Research Abstract |
Trimellitic anhydride (TMA) causes lung injury by inhalation in humans. In order to investigate the mechanism of lung injury by TMA, an experimental animal model was established. Guinea pigs were intramuscularly injected with trimellitated bovine serum albumin (TM BSA) with complete Freund's adjuvant (CFA). Appreciable amounts of antibodies against TM epitopes were detected in the sera of these animals. Guinea pigs that were passively sensitized with anti-TM antisera as well as the actively immunized animals developed hemorrhagic pneumonitis after TMA inhalation. It is well recognized that hyperimmune antisera of guinea pigs contain two subclasses of IgG antibodies. IgG1 and IgG2, which are known as homocytotropic and heterocytotropic antibodies. respectively. To determine the role of these antibodies in the airway injury with alveolar hemorrhages, they were isolated by gel filtration and by ion exchange column chromatography, and the guinea pigs that were sensitized with each of these
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antibodies were exposed to TMA inhalation.
The extent of lung injury in these animals was quantitatively determined by the measurements of lung extravasation of Evans blue dye injected intravenously after TMA inhalation. Significant increases in the extravasation of dye were observed in both animal groups sensitized with IgG1 and IgG2 antibodies.
In addition, results obtained with heat-treated antisera and IgG1 anbody did not significantly differ from those obtained with untreated samples. These results suggest that the lung injury resulting from TMA inhalation can be induced with humoral antibodies, not only IgG1 but also IgG2, and that at least two types of allergic reactions are involved in the pathogenesis of lung injury.
Next we assessed the role of sensitization in the development of bronchial hyperresponsiveness, and the relationship between bronchial responsiveness and bronchial inflammation. Fouteen guinea pigs were sensitized with lmg/0.5ml of TM_<36>-BSA and CFA on the first day as the priming dose and boosted on 15th day. By 28th day, all of the sensitized animals showed high passive hemagglutination titer against trimellited ovalbumin (TM-OVA). On 29th day. they were challenged by an inhalation of TMA (150mg/m^3) for 30 minutes and the respiratory resistance (Rrs) was monitored by oscillation method. In all sensitized animals, the Rs increased immediately after challenge and returned to baseline within six hours. The bronchial reactivity to acethylcholine (Ach), measured six hours after TMA challenge increased significantly compared to that 24 hours before challenge. There was also significant difference in the number of eosinophils in the bronchial mucosa of six and 24 hours after inhalation challenge. The increased airway responsiveness to Ach was correlated with the increase in the number of eosinophils in the bronchial epithelium. These results suggest that humoral antibody and eosinophils are involved in the development of TMA -induced asthma. Less
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