The effect of two muramyl
dipeptides,
N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP) and N-acetylmuramyl-D-alanyl-D-
isoglutamine (MDP(
D-D)), on the in vitro growth of two murine ascitic
plasmacytomas,
MOPC 173 and TEPC 15, and on an ascitic
lymphoma cell line, ABPL2, was studied. The ability of the muramyl
dipeptides to inhibit
tumor cell growth was compared with a sonicated antigenic preparation of Mycobacterium vaccae (
Vaccin), known to have macrophage stimulation activity. The growth of all three ascitic cell lines was inhibited by both muramyl
dipeptides and
Vaccin. Macrophage-depletion of the ascitic cell populations led to an increase in cell growth of TEPC 15 and
MOPC 173, and a decrease in ABPL2. A reduction or loss of the inhibitory activity of the muramyl
dipeptides or
Vaccin was also observed, and no inhibitory activity was found when the tumor cell lines were cultured in vitro to render them macrophage-free. The inhibitory activity of MDP or MDP(
D-D) was restored when purified ascitic macrophages were added to the in vitro cultured cell lines. It was demonstrated that a minimum number of macrophages were necessary for the expression of inhibitory activity.
Indomethacin, a PG-
synthetase inhibitor, was found to act in a synergistic manner with MDP and MDP(
D-D) in inhibiting TEPC 15, but antagonized the effect of these two agents on ABPL2. The
lymphoma cell line ABPL2 appeared to be the most sensitive to inhibition by MDP(
D-D), a nonpyrogenic, adjuvant-inactive stereoisomer of MDP.