In situ activation of mouse alveolar macrophages by aerosolized liposomal IFN-gamma and muramyl tripeptide

Interferon-gamma (IFN-gamma) was entrapped with an efficiency of 30-40% in muramyl tripeptide-containing liposomes by a freeze-thawing procedure. A microcytotoxicity assay was developed to measure the tumoricidal activity of mouse alveolar macrophages (AM) against tumoral target cells with a colorimetric viability test. Free IFN-gamma and liposomal muramyl tripeptide phosphatidylethanolamine (MTP-PE) were found to be only slightly effective to activate in vitro AM, whereas encapsulation of both INF-gamma and MTP-PE within the same liposomes produced higher activation of AM. Aerosolized IFN-gamma and liposomal immunomodulators enhanced antitumor properties of AM recovered in mice 24 h postinhalation. Whereas free IFN-gamma also induced a substantial activation of peritoneal macrophages, liposomal encapsulation significantly reduced the systemic activity of inhaled immunomodulators. This approach provides a useful model for the compartmentalized organ-specific activation of AM in mice.