|Budget Amount *help
¥2,100,000 (Direct Cost : ¥2,100,000)
Fiscal Year 1992 : ¥600,000 (Direct Cost : ¥600,000)
Fiscal Year 1991 : ¥1,500,000 (Direct Cost : ¥1,500,000)
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.