| Project/Area Number |
05044180
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Institution | Institute of Tropical Medicine, Nagasaki University |
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Principal Investigator |
NAKAMURA Michio Institute of Tropical Medicine, Nagasaki University, 熱帯医学研究所, 教授 (30091276)
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| Co-Investigator(Kenkyū-buntansha) |
RADEKE H.H. ハノーバー医科大学, 上級研究員
VERHOEVEN AJ オランダ赤十字中央研究所, 研究員
JONES O.T.G. ブリストル大学, 医学部, 教授
KUMATORI Atsushi Institute of Tropical Medicine, Nagasaki University, 熱帯医学研究所, 講師 (60244092)
KOSAKA Mitsuo Institute of Tropical Medicine, Nagasaki University, 熱帯医学研究所, 教授 (30079983)
ITAKURA Hideyo Institute of Tropical Medicine, Nagasaki University, 熱帯医学研究所, 教授 (00010512)
OTG Jones Bristol University (Great Britain)
HH Radeke Hannover Medical College (Germany)
AJ Verhoeven Central Laboratory of the Netherlands Red Cross Transfusion Service
RADEKE H ハノーバー医科大学, 上級研究員
JONES OTG 英国ブリストル大学, 教授
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| Project Period (FY) |
1993 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 1994: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1993: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | Superoxide-Generating System / Phagocytes / B Lymphocytes / Chronic granulomatoous disease / Cytochrome b558 / 活性酸素産生 |
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| Research Abstract |
1. For characterizing superoxide-generating system of phagocytes, we analyzed the cells of the patients with chronic granulomatous disease (CGD), because their genetic backgrounds have apparently well understood. The system is composed of 4 components, namely gp91-phox, p22-phox, p47-phox, and p67-phox. The former two make a cytochrome b558 lying on the membrane of phagocytes. In a patient, a common genetic phenotype has been noted to prevail over all kinds of his phagocytes. We, however, have discovered a 62-year male patient whose granulocyte fraction definitely contain a small population with normal amount of surface cytochrome b558. The population has been identified as eosinophils. Neither gp91-phox nor phorbol ester-stimulated chemiluminescence (CL) response are observed in his neutrophils and monocytes. His eosinophils definitely contain gp91-phox and exhibit the normal extent of CL response. Molecular analyzes have shown that coding sequences of his gp91-phox mRNA and its gene, and the poly (A) signal of the gene are normal. We have discovered a point mutation in the 5'-flanking region of his gp91-phox gene and are now extensively characterizing the function of that mutated region.
2. For characterizing superoxide-generating system of non-phagocytic cells, we used B lymphocytes, fibroblasts, mesangial cells, and others. The system of B lymphocytes is essential' the same as that of phagocytes. The expression of gp91-phox in B lymphocytes should be the same as that of neutrophils and monocytes but not of eosinophils. The amount of cytochrome b558 in B lymphocytes is quite low comparing to that of granulocytes, which corresponds to low CL response of the lymphocytes. Fibroblasts may have a different cytochrome because the cells of the patient with CGD normally generate superoxide anions. The superoxide-generating system of non-phagocytic cells should be hereafter reexamined by using molecular probes prepared for phagocytic cells.
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