Liposomal Muramyl Tripeptide Phosphatidylethanolamine (MTP-PE) Promotes Haemopoietic Recovery in Irradiated Mouse

Abstract

Pretreatment of C57B1/6 mouse with the macrophage activator muramyl tripeptide phosphatidylethanolamine encapsulated in liposomes (MTP-PE/MLV) induced haemopoietic recovery in subsequently irradiated mouse. An optimal endoCFU-S survival was observed when 200 μg MTP-PE/MLV was administered i.p. 24 h before irradiation. MTP-PE/MLV did not affect the day 8 exogenous CFU-S survival in the bone marrow immediately after irradiation. However, 3, 6, 9 and 14 days after irradiation the number of day 8 CFU-S was almost 2 to 4-fold higher in the bone marrow of the MTP-PE/MLV injected mouse. Also, recovery of the GM-CFC pools in femoral bone marrow after irradiation proceeded at a faster rate in the MTP-PE/MLV-treated animal than in control groups. After a single i.p. injection of MTP-PE/MLV to the non-irradiated mouse, the number of CFU-S in bone marrow was not significantly different from controls, whereas the number of GM-CFC was significantly increased. In addition, the percentage of day 8 CFU-S and GM-CFC in S-phase of the cell cycle was significantly increased, as was colony-stimulating activity present in the serum of treated animals. Pretreatment with MTP-PE/MLV protected the C57B1/6 mouse in a dose-dependent manner from the lethal effects of ionizing radiation. A single dose (100 or 200 μg) injected i.p. 24 h, or 100 μg MTP-PE/MLV injected i.v. 24 h before 9·5 Gy γ-rays protected 47, 85 and 59% of C57B1/6 mouse, respectively. The dose reduction factor in the case when the MTP-PE/MLV (24 h) and indomethacin (24 and 3 h) to mouse prior to irradiation exerted an additional radioprotective effect.