LIPOSOMAL MURAMYL TRIPEPTIDE PHOSPHATIDYLETHANOLAMINE (MTP-PE) PROMOTES HEMATOPOIETIC RECOVERY IN IRRADIATED MOUSE

Pretreatment of C57B1/6 mouse with the macrophage activator muramyl tr ipeptide phosphatidylethanolamine encapsulated in liposomes (MTP-PE/ML V) induced haemopoietic recovery in subsequently irradiated mouse. An optimal endoCFU-S survival was observed when 200 mu g MTP-PE/ MLV was administered i.p. 24h before irradiation. MTP-PE/MLV did not affect th e 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 th e MTP-PE/MLV injected mouse. Also, recovery of the GM-CFC pools in fem oral bone marrow after irradiation proceeded at a faster rate in the M TP-PE/MLV-treated animal than in control groups. After a single i.p. i njection of MTP-PE/MLV to the non-irradiated mouse, the number of CFU- S in bone marrow was not significantly different from controls, wherea s the number of GM-CFC was significantly increased. In addition, the p ercentage of day 8 CFU-S and GM-CFC in S-phase of the cell cycle was s ignificantly increased, as was colony-stimulating activity present in the serum of treated animals. Pretreatment with MTP-PE/MLV protected t he C57B1/6 mouse in a dose-dependent manner from the lethal effects of ionizing radiation. A single dose (100 or 200 mu g) injected i.p. 24h , or 100 mu g MTP-PE/MLV injected i.v. 24h before 9.5 Gy gamma-rays pr otected 47, 85 and 59% of C57B1/6 mouse, respectively. The dose reduct ion factor in the case when the MTP-PE/MLV (200 mu g per mouse) was ad ministered i.p. at that time was 1.17 (95% CL 1.13, 1.21). Combined ad ministration of MTP-PE/MLV (24h) and indomethacin (24: and 3h) to mous e prior to irradiation exerted an additional radioprotective effect.