ACTIVATION OF A DISTINCT SUBPOPULATION OF PULMONARY MACROPHAGES FOLLOWING EXPOSURE TO BIOLOGICAL RESPONSE MODIFIERS

A distinct subpopulation of tissue-associated pulmonary macrophages (T APM) displayed tumoricidal activity towards syngeneic and xenogeneic t argets following in vitro incubation with N-acetylmuramyl-L-alanyl-D-i soglutamine (MDP). This subpopulation, as well as, the predominant pop ulation 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 i n vivo tumoricidal activation of both populations of pulmonary macroph age was most effective when delivered either intravenously or via osmo tic 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. administer ed S-MDP. Under comparable conditions, IFN-alpha was not nearly as eff ective. Metabolic activation of TAPM, assessed by the release of incre ased 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 augmente d the release of superoxide observed at 24 hrs. Our results collective ly demonstrated that a subpopulation of lung macrophage, a tissue-asso ciated pulmonary macrophage, may be activated to a tumoricidal state a nd to release pronounced levels of oxygen free radicals following eith er in vitro or in situ treatment with several biological response modi fiers.