Altered membrane trafficking in activated bone marrow-derived macrophages

Activation of macrophages with interferon-gamma (IFN-gamma) and lipopolysac charide (LPS) leads to increased intracellular resistance to microbes and i ncreased major histocompatibility complex class II-restricted antigen prese ntation, processes that both use the vacuolar compartment. Despite the requ irement of the macrophage vacuolar compartment for microbicidal activities and antigen processing, the rates of endocytosis and membrane trafficking i n activated macrophages are not clearly defined. In this study, vacuolar co mpartment dynamics were analyzed in murine bone marrow-derived macrophages activated with LPS and/or IFN-gamma, conditions that increased macrophage n itric oxide production and resistance to infection by Listeria monocytogene s, Relative to nonactivated cells, activated macrophages showed diminished rates of fluid-phase pinocytosis and phagocytosis and delayed progression o f macropinosomes and phagosomes to late endosomes and lysosomes, In contras t to the slowing of membrane trafficking, rates of macropinosome acidificat ion were similar between activated and nonactivated cells. One consequence of this slowed membrane trafficking in activated macrophages was a prolonge d exposure of incoming molecules to an acidic nonlysosomal compartment, a c ondition which may facilitate microbicidal chemistries or antigen processin g.