1990 Fiscal Year Final Research Report Summary
Mechanism of Active Oxygen Generation in Neutrophils and Its Role in Defense Against Bacterial Infection
| Project/Area Number |
01480175
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
細菌学
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| Research Institution | The Institute of Medical Science, the University of Tokyo |
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Principal Investigator |
KANEGASAKI Shiro Inst. of Med. Sci. Univ. of Tokyo, Professor, 医科学研究所, 教授 (10012767)
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| Co-Investigator(Kenkyū-buntansha) |
ONO Yasuo Teikyo Univ. Sch. of Med., Internal Medicine, Resident, 医学部・内科, 助手 (10177272)
UENO Ikuko Inst. of Med. Sci. Univ. of Tokyo, Research Associate, 医科学研究所, 助手 (60012738)
NAKAMURA Michio Inst. of Med. Sci. Univ. of Tokyo, Associate Professor, 医科学研究所, 助教授 (30091276)
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| Project Period (FY) |
1989 – 1990
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| Keywords | Neutrophils / Macrophages / Superoxide anion / Lymphocytes / Chronic Granulomatous Disease / Spin-trap ESR |
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| Research Abstract |
Previously, we have shown that almost all molecular oxygen consumed during the respiratory burst is converted to superoxide anion, which is released to the outside of neutrophils (or inside of phagosomes). By using spin-trap EPR spectrometry, we confirmed that superoxide anion but not hydroxyl radial was formed during the respiratory burst induced by soluble or particulate stimuli. We have developed monoclonal and polyclonal antibodies against large and small subunits of cytochrome b_<558>, which is considered to be involved in the reaction. Using these antibodies, we found that the cytochrome was present in the plasma membrane of neutrophils, eosinophils, monocytes and macrophages in various tissues and B lymphocytes, all of which could generate superoxide anion upon stimulation. We have also established a method for the prenatal diagnosis of cytochrome b_<558>-deficient chronic granulomatous disease and its carrier state. We found that the antibiotic cerulenin inhibited the respiratory burst in neutrophils and macrophages through inhibition of intracellular calcium mobilization. We monitored whole blood chemiluminescence in severely burned patients and found that the opsonizing capacity in the blood is decreased in these patients due to decreased levels of complement, immunoglobulins and fibronectin. Such monitoring was effective for the determining the contents and quantity of colloidal infusion during the treatments. Introduction of the controlled treatment to burned patients lowered the mortality rate of burned patients to 25% from the 60.9% for the 2 years before the introduction of the treatment.
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