Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan
Correspondence: Joel A. Swanson, Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109-0620. E-mail: jswan{at}umich.edu
Activation of macrophages with interferon-
(IFN-) 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-, 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.
Key Words: macrophages • activation • Listeria monocytogenes • lipopolysaccharide • interferon- • lysosome
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