Activation of a distinct subpopulation of pulmonary macrophages following exposure to biological response modifiers.

Abstract

A distinct subpopulation of tissue-associated pulmonary macrophages (TAPM) displayed tumoricidal activity towards syngeneic and xenogeneic targets following in vitro incubation with N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP). This subpopulation, as well as, the predominant population of freely lavagable alveolar macrophages destroyed allogeneic targets following a similar incubation with either 6-0-stearoyl MDP (S-MDP) or recombinant interferon-gamma (IFN-gamma). IFN-gamma-induced in vivo tumoricidal activation of both populations of pulmonary macrophage was most effective when delivered either intravenously or via osmotic minipump infusion and least effective when administered by direct intratracheal instillation. The separate populations also displayed in vivo activation in response to liposome-encapsulated i.v. administered S-MDP. Under comparable conditions, IFN-alpha was not nearly as effective. Metabolic activation of TAPM, assessed by the release of increased levels of superoxide free radicals during phagocytosis, occurred following 24 hr exposure to S-MDP or lipopolysaccharide. Incorporation of these agents into multilamellar vesicle liposomes further augmented the release of superoxide observed at 24 hrs. Our results collectively demonstrated that a subpopulation of lung macrophage, a tissue-associated pulmonary macrophage, may be activated to a tumoricidal state and to release pronounced levels of oxygen free radicals following either in vitro or in situ treatment with several biological response modifiers.