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Published on: August 26, 2016
Molecular aspects of microparticle phagocytosis by dendritic cells
Mutsumi Yoshida1, Julia E Babensee
1Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, 313 Ferst Drive, Atlanta, GA 30332, USA.
Abstract:
The ability of immature dendritic cells (iDCs) derived from human peripheral blood mononuclear cells to phagocytose poly(lactic-co-glycolic acid) (PLGA) microparticles (MPs) as compared to polystyrene MPs and the molecular aspects of this phagocytosis were investigated. Treating iDCs with PLGA or polystyrene fluorospheres of approximately 3 microm in diameter resulted in the internalization of the particles as evidenced by confocal laser scanning micrographs. This uptake of fluorospheres by DCs was decreased by pretreatment of cells with cytochalasin D or by incubation with the fluorospheres at 4 degrees C, and was sensitive to EDTA and trypsin pretreatments in a dose-dependent manner. In agreement with our previous studies, treatment of iDCs with PLGA MPs, but not with polystyrene MPs, led to DC maturation, as measured by increase in release of the autocrine maturation cytokine, tumor necrosis factor-alpha, which was dependent on ratio of PLGA MPs to DCs. Taken together, this work begins to address the role of phagocytosis on PLGA MP-induced DC maturation and the molecular mechanisms involved.
Insights
Immature dendritic cells (iDCs) phagocytose poly(lactic-co-glycolic acid) (PLGA) microparticles, a process crucial for PLGA-induced DC maturation. This study explores the molecular mechanisms underlying this phagocytosis and its role in DC maturation.
Area of Science:
- Immunology
- Biomaterials Science
- Cell Biology
Background:
- Dendritic cells (DCs) are key immune regulators.
- Microparticles (MPs) are used in drug delivery and research.
- Understanding DC interaction with biomaterials is crucial for therapeutic applications.
Purpose of the Study:
- To investigate the phagocytosis of poly(lactic-co-glycolic acid) (PLGA) microparticles by immature dendritic cells (iDCs).
- To compare PLGA microparticle uptake with polystyrene microparticles.
- To elucidate the molecular mechanisms of microparticle phagocytosis and its role in DC maturation.
Main Methods:
- Treatment of iDCs with PLGA and polystyrene fluorospheres.
- Confocal laser scanning microscopy for visualizing particle internalization.
- Inhibition studies using cytochalasin D, low temperature, EDTA, and trypsin.
- Measurement of tumor necrosis factor-alpha release to assess DC maturation.
Main Results:
- iDCs successfully phagocytosed both PLGA and polystyrene microparticles.
- Phagocytosis was dependent on cellular energy, temperature, and cell surface proteins.
- PLGA microparticles, but not polystyrene, induced iDC maturation, evidenced by increased TNF-α release.
- PLGA microparticle-induced maturation was dependent on the microparticle-to-DC ratio.
Conclusions:
- Phagocytosis is a key mechanism for iDC interaction with PLGA microparticles.
- PLGA microparticles induce iDC maturation through phagocytosis, involving specific molecular pathways.
- This research provides insights into the immunomodulatory potential of PLGA-based biomaterials.
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