Potential value of liposomes containing muramyl dipeptide for augmenting the tumoricidal activity of human alveolar macrophages.

Potentiation of the tumoricidal activity of human alveolar macrophages (AM) by muramyl dipeptide (MDP) and MDP in liposomes (liposome-MDP) was examined. Significant increase in AM-mediated cytotoxicity against allogeneic melanoma cells required the interaction of AM with liposome-MDP for a minimum of 4 h. The uptake by human AM of liposomes containing fluorescent quinacrine was examined. A linear correlation was found between the amount of liposomes added to AM monolayers and their phagocytosis of liposome-entrapped quinacrine. Addition of phosphatidylserine to liposomes composed of phosphatidylcholine enhanced both the phagocytosis of liposomes and the ability of liposome-MDP to potentiate the tumoricidal activity of human AM. In experiments on the dose response of liposomes containing 10 micrograms/ml MDP, 50 nmol of liposomes/10(5) AM caused maximal activation of human AM, and greater than 100 nmol of liposomes was less effective. These results show that multilamellar vesicle liposomes containing MDP are more effective than free MDP in potentiating the tumoricidal activity of human AM during culture for 4 h.