Synergism between human recombinant gamma-interferon and muramyl dipeptide encapsulated in liposomes for activation of antitumor properties in human blood monocytes.
Highly purified human blood monocytes, isolated by centrifugal elutriation under endotoxin-free conditions, were activated in vitro by combining subthreshold amounts of human recombinant gamma-interferon (r-IFN-gamma) and muramyl dipeptide (MDP) to become tumor cytotoxic against allogeneic A375 melanoma cells. Only intact r-IFN-gamma and MDP produced synergism for human monocyte activation. Neither pH 2-treated r-IFN-gamma and intact MDP nor heat-treated IFN-gamma and intact MDP, nor intact IFN-gamma and the biologically inactive stereoisomer of MDP, N-acetylmuramyl-D-alanyl-D-isoglutamine, produced activation of blood monocytes. The encapsulation of intact r-IFN-gamma and MDP within the same preparation of multilamellar liposomes was synergistic for monocyte activation. These data show that synergism for monocyte activation can be produced by human r-IFN-gamma and MDP produced synthetically can be simultaneously delivered to monocytes. Because both r-IFN-gamma and MDP can now be produced in large standardized quantities their synergism for activation of tumoricidal properties in human monocytes could be of clinical significance.
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000008:administration & dosage*; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004357:Drug Synergism; D006801:Humans; D007371:Interferon-gamma / Q000008:administration & dosage*; D008081:Liposomes; D008262:Macrophage Activation / Q000187:drug effects; D009000:Monocytes / Q000276:immunology*; D009374:Neoplasms, Experimental / Q000276:immunology*; D011994:Recombinant Proteins / Q000008:administration & dosage*
D008081:Liposomes; D011994:Recombinant Proteins; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D007371:Interferon-gamma