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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
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.
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.
- 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.