Stimulation of macrophages by muroctasin to produce colony-stimulating factors

Murocatasin (N2-[(N-acetylmuramoyl)-L-alanyl-D-isoglutaminyl]-N6-stearoyl-L-lysine, MDP-Lys(L18], a muramyl dipeptide derivative, has been reported to increase the number of peripheral granulocytes and monocytes after subcutaneous administration to animals and humans. When macrophage cell lines such as P388D1 and J774.1 cells were incubated with muroctasin in vitro, the production of colony-stimulating factor (CSF) from these cells was increased significantly. By Northern blot analysis, expression of the M-CSF gene, but not the G-CSF gene, in these macrophage cell lines was found to be enhanced by treatment with muroctasin. However, expression of the G-CSF gene in NFSA cells, a fibrosarcoma cell line established as a G-CSF producer, was actually enhanced by incubation with the conditioned medium from P388D1 cells stimulated with muroctasin. Thus, the hematopoietic activity of muroctasin was suggested to be attributable primarily to the enhanced production of M-CSF from macrophages. The enhanced G-CSF production from NFSA cells may be due at least to interleukin-1 released from muroctasin-stimulated macrophages.