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Related Experiment Videos

Altered membrane trafficking in activated bone marrow-derived macrophages.

A W Tsang1, K Oestergaard, J T Myers

  • 1Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor 48109-0620, USA.

Journal of Leukocyte Biology
|October 19, 2000
PubMed
Summary

Activated macrophages exhibit slower endocytosis and delayed vesicle trafficking, prolonging exposure to acidic compartments. This impacts microbial resistance and antigen presentation, crucial for immune responses.

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Area of Science:

  • Immunology
  • Cell Biology
  • Microbiology

Background:

  • Macrophage activation by interferon-gamma (IFN-gamma) and lipopolysaccharide (LPS) enhances antimicrobial and antigen-presenting functions.
  • These functions rely on the vacuolar compartment, but trafficking dynamics in activated macrophages are not well understood.

Purpose of the Study:

  • To investigate vacuolar compartment dynamics in murine bone marrow-derived macrophages activated with LPS and/or IFN-gamma.
  • To determine the impact of activation on endocytosis, membrane trafficking, and acidification.

Main Methods:

  • Murine bone marrow-derived macrophages were activated with LPS and/or IFN-gamma.
  • Rates of fluid-phase pinocytosis and phagocytosis were measured.
  • Progression of macropinosomes and phagosomes to late endosomes/lysosomes was tracked.

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  • Macropinosome acidification rates were assessed.

    • Main Results:

    • Activated macrophages showed significantly diminished rates of pinocytosis and phagocytosis compared to nonactivated cells.
    • The progression of macropinosomes and phagosomes to late endosomes and lysosomes was delayed in activated macrophages.
    • Despite slowed trafficking, macropinosome acidification rates remained similar between activated and nonactivated cells.

    Conclusions:

    • Macrophage activation by IFN-gamma and LPS slows membrane trafficking, leading to prolonged exposure of internalized molecules to acidic, nonlysosomal compartments.
    • This altered vacuolar dynamics may enhance intracellular microbicidal activity and major histocompatibility complex class II-restricted antigen presentation.