Grant-in-Aid for Overseas Scientific Survey.
|Research Institution||Nagoya City University School of Medicine|
OKADA Hidechika Nagoya City University School of Medicine, 医学部, 教授 (30160683)
DEVINE Dana. Canadian Red Cross Soci., Blood Transfusi, 研究室長
KAZATCHKINE Hopital Broussais, 教授
DIERICH Manf Inst. Hygine, 教授
SIMS Peter J Oklahoma Blood Inst., 研究部長
MORGAN B.Pau Univ. Wales Coll. Med., 研究室長
HOLMES Chris Uuiv. Bristol, 主任研究員
MULLERーEBERH Bernhard Nocht Inst., 研究所長
NUSSENZWEIG NeW York Univ. Med. Ctr., 教授
岡田 則子 福岡大学, 医学部, 助手 (20160682)
WILLIAM Cdmp 名古屋市立大学, 医学部, 助手 (00203422)
MCGEER Pdtri Univ. B. C, 教授
MORGAN B.Pou Univ. Wales Coll. Med., 研究室長
HOLMEG Chris Univ. Bristol, 主任研究員
NUSSENZWEPG New York Univ. Med. Ctr., 教授
MCGEER Patrick L. University of British Columbia
KAZATCHKINE Michel D. Hospital Broussais
MORGAN B. Paul University of Wales College of Medicine
VICTOR Nussenzweig New York University Medical Center
HOLMES Christopher H. University of Bristol
WILLIAM Campbell Nagoya City University School of Medicine
OKADA Noriko Fukuoka University School of Medicine
|Project Fiscal Year
1989 – 1991
Completed(Fiscal Year 1991)
|Budget Amount *help
¥10,800,000 (Direct Cost : ¥10,800,000)
Fiscal Year 1991 : ¥3,300,000 (Direct Cost : ¥3,300,000)
Fiscal Year 1990 : ¥3,000,000 (Direct Cost : ¥3,000,000)
Fiscal Year 1989 : ¥4,500,000 (Direct Cost : ¥4,500,000)
|Keywords||complement / HRF20 / DAF / 20kDa homologous restriction factor / CD59 / 補体 / homologous restriction factor / C8 binding protein / membrane / infection|
Complement system can discriminate invading microorganisms without antibodies. The mechanism to detect invaders is based on the detection of species specific inhibitors on self cell membranes where complement reaction is restricted. Since no such membrane inhibitors are present on invaders, complement reaction proceeds without restriction. As a membrane inhibitor, we have found 20kDa homlogous restriction factor (HRF20) which inhibits the terminal step of comlement reaction to form membrane attack complexes. lF5 is a monoclonal antibody against HRF20 and we analyzed ontogenical expression of HRF20 by use of immunohistochemical staining with lF5. Then we found that HRF20 is significantly expressed in fetal brain as well as endothelial cells and blood cells. By immunohistochemical analysis, we also found that HRF20 is significantly expressed at the diseased sites of brains from Alzheimer disease patients.
We also found that among CD8 bright T lymphocytes, there is a distinct population wh
ich express little, if any, of DAF (decay accelerating factor) and HRF20. Since this population express HLA-DR, which is regarded as a indication of T cell activation, the DAF negative CD8 bright T lymphocytes could be regarded as in a status of activated. If this is the case, activated T lymphocytes might be ready to eliminated by permitting complement activation.
Peripheral blood lymhocytes from HIV infected patients were analyzed for their expression in HRF20. We found that CD8 bright T lymphocytes in HIV-infected patients are decreased in expression of HRF20. However, we have no appropriate interpretation on this phenomenon.
We analyzed HRF20 gene of a patient who is genetically deficient in HRF20 expression. We found two single base deletion in his HRF20 gene and the deletions were homozygous. The patient's farther and mother were both heterozybosly deleted in the HRF20 gene as well as his sister.
We transfected cDNA of HRF20 into CHO. cells and HRF20 was expressed on the cells. The cells became resistant to human complement but not to mouse and rabbit complement indicating that the species specific reactivity in the HRF20 molecule might be at the peptide sequence but not at sacchardes. Less