1992 Fiscal Year Final Research Report Summary
Bio-molecular Approaches to Mycobacterial
| Project/Area Number |
03670209
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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 |
細菌学
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| Research Institution | Osaka University |
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Principal Investigator |
DOHI Yoshitane Osaka University Medical School Department of Bacteriology, Associate Professor, 医学部, 助教授 (10028574)
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| Project Period (FY) |
1991 – 1992
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| Keywords | Trehalose Mycolate / Macrophage Activation / Tuberculosis / Tumor Immunotherapy / Gamma-delta T Cells |
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| Research Abstract |
We isolated a mycolic acid-containing glycolipid, trehalose-2,3,6'-trimycolate ( TTM ) from an acid-fast bacterium, Gordona aurantiaca, and characterized its biological activity. Subcutaneous or intra-capsular (kidney) injection of the liposome-encapsulated preparation of TTM into mice generated similar histo-pathological changes at the injected sites as that at the infected foci of tubercle bacilli : Abscess formation with caesation necrosis, infiltration of macrophages and proliferation of fibroblasts around the abscess were observed in these lesions. Intravenous or intra-peritoneal injection of TTM-liposomes rendered peritoneal macrophages to be in an activated state. The activated macrophages lysed syngeneic tumor cells including mastocytoma, myeloma or lung cancer cells by cell-to-cell contact. In addition, they released inflammatory factors including hydrogen peroxide, interleukin-1 and tumor-necrosisfactor alpha, suggesting that the activated macrophages were playing a central role in caesation necrosis and/or abscess formation. Furthermore, this treatment was effective in vivo on tumor-bearing mice to prolong their survival times against intraperitoneal challenge of P815 mastocytoma cells or against metastatic Lewis' lung cancer cells in the lymph nodes.
We also found that in the peritoneal exudate cells of the mice, which were injected intraperitoneally with TTM-liposomes, not only activated macrophages but also gamma-delta T lymphocytes were generated in a large number. Fluorescein-activated cell sorter analyses of the lymphocytes fraction of the peritoneal exudate cells revealed the gamma-delta T cells co-expressed alpha-beta antigen receptors on their surfaces. In addition, these T cells augmented the intra-cellular killing of salmonella in macrophages.
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[Publications] Ohtsubo, Y., Furukawa, M., Imagawa, T., Sugimoto, N., Ikutoh M., Nakatsugi, S., Katoh, Y., Shinka, S. and Dohi, Y: "Growth inhibition of tumor cells by a liposome-encapsulated, mycolic acid-containing glycolipid, trehalose 2,3,6'-trimycolate" Immunology. 74. 497-503 (1991)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Ohtsubo, Y., Kiso, T., Isoda, M., Furukawa, M., Toya, H., Shinka, S., and Dohi, Y: "Immunological Activity of trehalose-2,3,6'-trimycolate" J. Pharmaco-Dyn. 14. 157 (1991)
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「研究成果報告書概要(欧文)」より
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[Publications] Dohi, Y., Sunada, S., Aoki, M., Moriguchi, A., Okabayashi, M., Miyata, M., and Matsuda, H: "Eradication of metastatic cancer cells from lymph nodes by local admonistration of anti-CD3 antibody" Cancer Immunology Immunotherapy. (1993)
Description
「研究成果報告書概要(欧文)」より
