title: Altered membrane trafficking in activated bone marrow-derived macrophages.
abstract: Activation of macrophages with interferon-gamma (IFN-gamma) and lipopolysaccharide (LPS) leads to increased intracellular resistance to microbes and increased major histocompatibility complex class II-restricted antigen presentation, processes that both use the vacuolar compartment. Despite the requirement of the macrophage vacuolar compartment for microbicidal activities and antigen processing, the rates of endocytosis and membrane trafficking in activated macrophages are not clearly defined. In this study, vacuolar compartment dynamics were analyzed in murine bone marrow-derived macrophages activated with LPS and/or IFN-gamma, conditions that increased macrophage nitric oxide production and resistance to infection by Listeria monocytogenes. Relative to nonactivated cells, activated macrophages showed diminished rates of fluid-phase pinocytosis and phagocytosis and delayed progression of macropinosomes and phagosomes to late endosomes and lysosomes. In contrast to the slowing of membrane trafficking, rates of macropinosome acidification were similar between activated and nonactivated cells. One consequence of this slowed membrane trafficking in activated macrophages was a prolonged exposure of incoming molecules to an acidic nonlysosomal compartment, a condition which may facilitate microbicidal chemistries or antigen processing.
authors.affiliation: Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor 48109-0620, USA.
authors.forename: A W
authors.initials: AW
authors.lastname: Tsang
authors.forename: K
authors.initials: K
authors.lastname: Oestergaard
authors.forename: J T
authors.initials: JT
authors.lastname: Myers
authors.forename: J A
authors.initials: JA
authors.lastname: Swanson
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects; D001692:Biological Transport; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D003594:Cytoplasmic Granules / Q000648:ultrastructure; D004705:Endocytosis / Q000187:drug effects; D011992:Endosomes / Q000502:physiology; D005260:Female; D006863:Hydrogen-Ion Concentration; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008089:Listeria monocytogenes / Q000502:physiology; D008247:Lysosomes / Q000502:physiology; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism* / Q000382:microbiology / Q000648:ultrastructure; D008561:Membrane Fusion; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D010587:Phagocytosis / Q000187:drug effects; D010588:Phagosomes / Q000502:physiology; D010873:Pinocytosis / Q000187:drug effects; D011994:Recombinant Proteins; D014617:Vacuoles / Q000502:physiology; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse