Studies of human alveolar macrophages ( Functional aspects )
| Project/Area Number |
60570347
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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 | Kyoto University |
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Principal Investigator |
YAMAMOTO Kokichi Chest disease research institute, Kyoto university , Assistant, 結核胸部疾患研究所, 助手 (10166796)
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| Co-Investigator(Kenkyū-buntansha) |
SASADA Masataka Faculty of medicine, Kyoto university , Assistant, 医学部, 助手 (30144364)
KUZE Fumiyuki Chest disease research institute, Kyoto university, Professor, 結核・胸部疾患研究所, 教授 (10027104)
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| Project Period (FY) |
1985 – 1986
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| Project Status |
Completed (Fiscal Year 1986)
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| Budget Amount *help |
¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1986: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1985: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | Alveolar macrophages / Phagocytosis / Candidacidal activity / Interferon-gamma / Oxygen radicals / Respiratory burst / Protein kinase C / 単球由来マクロファージ |
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| Research Abstract |
Uptake, killing, and killing mechanism of human alveolar macrophages (AM) were explored usingCandida parapsilosis (CP) as a test organism. Effects of recombinant interferon- <gamma> (rIFN- <gamma> ) were also examined. AM obtained by bronchoalveolar lavage were cultured on culture plates in MEM containing 10% heat-inactivated human AB serum. Through cultivation up to day 7, more than 90% of AM ingested CP. A small but significant number of CP were killed. The killing activity was enhanced by addition of rIFN- <gamma> during culture. Release of <O_2^-> from AM declined at first, increased through day 3 to day 5 and then decreased. Addition of rIFN- <gamma> primed AM to release more <O_2^-> and <H_2O_2> . The effect was dose-dependent and more than 10U/ml of rIFN- <gamma> was required. Autoclved rIFN- <gamma> did not have any effect. These findings indicate that AM were activated in vitro by rIFN- <gamma> in the presence of serum. IFN- <gamma> might be a useful tool for treatment of infe
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ctious diseases in compromized hosts or malignant processes through activation of AM in vivo. Oxygen radicals seemed to be important for killing of CP since candidacidal activity of AM was strongly inhibited by superoxide dismutase.
Properties of oxygen radical generation were further explored using AM from normal and BCG-injected mice. BCG AM released more <O_2^-> when stimulated with zymosan or E(IgG) than normal AM. In contrast, when stimulated with Phorbol myristate acetate (PMA), such enhancement was not observed. Such characteristic that AM did not release a large amount of <O_2^-> to every stimulus may suggest a maturation or adaptation of AM in vivo. AM released only a small amount of <O_2^-> when stimulated with dioctanoyl glycerol plus A23187. These findings suggest that PMA receptor activity or signal transduction pathway from the receptor to <O_2^-> generating system of AM might be different from those of peritoneal macrophages. Normal mouse AM cultured in vitro were activated by the culture supernatant of Con A-stimulated spleen cells.
Candidacidal activity or oxygen radical generation of human monocyte-derived macrophages was similar to those of human AM. It may be benificial to use monocytes to examine functional aspects of human macrophages. Less
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Report
(1 results)
Research Products
(19 results)
