LIPOSOME-ENCAPSULATED MURAMYL TRIPEPTIDE UP-REGULATES MONOCYTE CHEMOTACTIC AND ACTIVATING FACTOR GENE-EXPRESSION IN HUMAN MONOCYTES AT THE TRANSCRIPTIONAL AND POSTTRANSCRIPTIONAL LEVELS

Liposome-encapsulated muramyl tripeptide phosphatidylethanolamine (L-M TP-PE) is a novel immune modulator that is now under investigation aga inst metastatic melanoma and osteosarcoma. We have already reported th at L-MTP-PE induced monocyte-mediated tumoricidal activity and up-regu lation of the tumor necrosis factor and interleukin-1 (IL-1) in vivo a nd in vitro. We now demonstrate that L-MTP-PE also induces monocyte ch emotactic and activating factor (MCAF) mRNA expression at both the tra nscriptional and post-transcriptional levels. Monocyte chemotactic act ivity was also present in the supernatants of L-MTP-PE-stimulated cell s. In monocytes, the increased expression of MCAF was induced rapidly (by 2 h) but was short-lived. By 4 h, MCAF mRNA had decreased to backg round level. We found no change in MCAF mRNA levels in lymphocytes exp osed to L-MTP-PE. We therefore conclude that L-MTP-PE selectively up-r egulates MCAF expression in monocytes and that MCAF may play a role in the tumoricidal and immune-stimulating activity of L-MTP-PE.