Modulation of the growth of murine thymoma cell lines having different lyt-phenotypes by MDP and MDP(D-D): Macrophage-mediated inhibition of in vitro cell growth

The ability of N-acetylmuramyl-l-alanyl-d-isoglutamine (MDP) and its adjuvant-inactive stereoisomer, N-acetylmuramyl-d-alanyl-d-isoglutamine, (MDP(D-D)) to inhibit the in vitro growth of 3 murine ascitic thymoma lines, expressing different Lyt-phenotypes, was studied. MDP inhibited the growth of all 3 cell lines. MDP(D-D) inhibited the 2 cell lines expressing Lyt-1+2− or Lyt-1+2+ phenotypes, but not the third cell line which expressed the Lyt-1−2+ phenotype. The ability of MDP or MDP(D-D) to inhibit thymoma growth was lost when the ascitic cell populations were depleted of macrophages. MDP could be replaced by a supernatant derived from an ascitic Lyt-1+2− cell population exposed to MDP. The supernatant required the presence of macrophages for activity. The inhibition by MDP of the growth of the Lyt-1−2+ cell line was prostaglandin synthetase dependent: indomethacin antagonized the inhibitory activity of MDP. The inhibition by MDP of the Lyt-1+2− cell line was partially antagonized by indomethacin, and no antagonism was observed with the Lyt-1+2+ cell line.