Inhibition of cilia regeneration of Tetrahymena by ansamitocins, new antitumor antibiotics.
Ansamitocins inhibited cilia regeneration of partially deciliated Tetrahymena pyriformis W, and the activity depended on the acyl groups at the C3 position.
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Ansamitocins inhibited cilia regeneration of partially deciliated Tetrahymena pyriformis W, and the activity depended on the acyl groups at the C3 position.
Desdanine inhibited the plaque formation of male-specific coliphages but not that of other coliphages tested. Desdanine also suppressed the multiplication of both RNA phage Q beta and filamentous DNA phage f1 at the concentration of 3.13 approximately 6.25 mug/ml which had no influence on the growth of their host cells. However, the inhibitory effect on the phage multiplication was not due to the inactivation of phage particles nor the prevention of phage adsorption and penetration into the host cells. Desdanine also inhibited the transfer of R plasmid, R 100-1, in E. coli at 6.25 approximately 12.5 mug/ml without affecting the viability of donor and recipient cells.
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TAN-1511 A, a microbial lipopeptide, stimulates granulocytopoiesis through the induction of various hematopoietic cytokines. The ability of synthetic TAN-1511 A to affect megakaryocytopoiesis was examined. TAN-1511. A augmented the activity of acetylcholine esterase (AChE), which is a cell-lineage marker enzyme of megakaryocytes in cultured murine bone marrow cells and enhanced megakaryocyte colony formation in fibrin clot culture. These effects were observed not only in the presence, but also in the absence of IL-3, which is a megakaryocyte colony-stimulating factor. The increase in AChE activity mediated by TAN-1511 A was blocked by anti-IL-6 but not anti-IL-3 or anti-GM-CSF neutralizing antibodies. RT-PCR analysis also showed that the remarkable induction of IL-6 was triggered by treatment with TAN-1511 A, while each message level of c-mpl ligand and c-mpl remained unchanged, suggesting that the IL-6 induced by the lipopeptide plays a role in enhanced megakaryocytopoiesis. TAN-1511 A also stimulated the proliferation of CMK86, a human megakaryoblastic cell line. This promoted growth was partially and additively affected by anti-IL-3, anti-IL-6, and anti-GM-CSF antibodies. TAN-1511 A slightly reduced the expression of GpIb and GpIIb/IL1a in CMK86 cells. The enhanced platelet recovery mediated by TAN-1511 A was also demonstrated in a model of myelosuppressive mice. These results suggest that TAN-1511 A directly affects megakaryocytopoiesis, and indirectly modulates megakaryocytopoiesis through the induction of cytokines such as IL-6.