1989 Fiscal Year Final Research Report Summary
Studies on the analysis of molecular structure and signal-transduction mechanism of the cell-membrane damaging by staphylococcal cytolytic toxins.
| Project/Area Number |
63480150
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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 | Chiba University |
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Principal Investigator |
KATO Iwao Chiba University, School of Medicine, Professor, 医学部, 教授 (40012702)
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| Co-Investigator(Kenkyū-buntansha) |
KAMIO Yoshiyuki Tohoku University, Faculty of Agriculture Assistant Professor, 農学部, 助教授 (00109175)
MORINAGA Naoko Chiba University, School of Medicine Assistant, 医学部, 助手 (20092108)
NODA Masatoshi Chiba University, School of Medicine Assistant Professor, 医学部, 助教授 (60164703)
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| Project Period (FY) |
1988 – 1989
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| Keywords | Staphylococcal alpha-toxin / Leukocidin S and F comp. / ADP-ribosyltransferase / Phospholipase A_2 / Phospholipase C / GTP-binding protein / HL-60 cells / ヒト前骨髄性白血病HL-60細胞 |
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| Research Abstract |
1. After binding of the highly purified staphylococcal alpha-toxin to rabbit erythrocyte or polymorphonuclear leukocyte (neutrophile) membranes, the alpha-toxin rapidly stimulated the activities of phospholipase A_2 and inositol phospholipid specific phospholipase C, respectively, in the presence of NAD and GTP. Thereafter, it was shown that 37 K and 41 K GTP-binding proteins ADP-ribosylated by the ADP-ribosyltransferase of the alpha-toxin transmitted the activating signal to these phospholipases A_2 and C.
2. Staphylococcal leukocidin consists of two components (S and F) which are inactive when tested alone, but act synergistically to cause lysis of ngutophiles and macrophages of rabbits and humans. An ADP,-ribosylation of 37 K GTP-binding protein by the S component which possesses an ADP-ribosyltransferase activity resulted in the stimulation of phospholipase A_2 activity in the presence of NAD and GTP.
3. Staphylococcal leukocidin F component having an ADP-ribosyltransferase stimulated the activity of inositol phospholipid specific phospholipase C in the presence of NAD and GTP resulting from the ADP-ribosylation of a molecular weight of 41 K GTP-binding protein by the F component.
The susceptibility of human promyelocytic leukamia HL-60 cells to the cytotoxic activity of leukocidin changed depending on the degree of differentiation induced by TPA. The cytotoxic activity of HL-60 cells treated with TPA for 6 hours was more required for a 50-fold dose of leukocidin than that of the mature macrophage-like cells have been treating with TPA for 36 hours.
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