| Project/Area Number |
04454197
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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 |
植物保護
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| Research Institution | National Institute of Health |
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Principal Investigator |
SATO Hiroko National Institute of Health, Department of Bacteriology, Chief, 細菌部, 室長 (80100080)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAKAWA Yoshio National Institute of Health, Department of Cytochemistry, Senior Researcher, 細胞化学部, 主任研究官 (50100102)
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| Project Period (FY) |
1992 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1994: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1993: ¥700,000 (Direct Cost: ¥700,000)
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| Keywords | Pertussis toxin / Leukocytosis / Monoclonal antibody / Adhesion factor / Mouse encephalopathy / リンパ節細胞 / 百白咳毒素 / 白血球増夛症 / セレクチン |
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| Research Abstract |
Pertussis toxin consisting of five different subunits (S1-S5) induces diverse and unique biological activities in endocrine, immune, and nervous systems. The subunit structure of pertussis toxin (PT) is well defined, but a role of each subunit in the pathophysiological activities is still unclear. The ADP-ribosyl-transferase activity of the S1 to G-protein is essential for most of major biological or toxic activities of PT.Although the B oligomer (S2-S5) is known as a binding protein, the each subunit in the B oligomer must play rather complex roles to produce the various unique PT activities.
In this study, roles of each subunit of PT as adhesin and signal transducer in leukocytosis promotion and encephalopathy induction were explored. For this purpose, the mouse monoclonal antibodies against each subunit of PT were utilized as a major powerful tool through the experiments. Leukocytosis caused by intravenous (iv) injection of PT was suppressed by administration of not only anti-S1 but
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also anti-B monoclonal antibodies even at three days after the iv injections. This results suggest that PT on acceptor cells is still able to interact with the antibody after the time when the leukocytosis already occurred and that unhoming leukocytes in the peripheral blood may be able to home by the PT-neutralization with the antibody. Similar results were obtained by the iv injection of lymphocytes treated with PT in vitro. Some preliminary experimental data are accumulating to investigate the interaction between the lymphocytes and endothelial cells of mice in vivo and in vitro. Further, encephalopathy and leukocytosis induced by the intracerebral (ic) injection of PT in mice were also neutralized with the antibody administered by iv injection, but some anti-S1 or anti-S2 antibodies which were not able to neutralize the leukocytosis inhibited the induction of the encephalopathy. The S2 and S3 seems to play different and specific role through adherence to cell receptors. And S4 may contribute to stabilization of some signal transduction to the cell membrane and translocation of active part of S1 to an active site at and/or after the binding step. Less
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