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Updated: May 4, 2026
Isolation and Characterization of Neutrophil-derived Microparticles for Functional Studies
Published on: March 2, 2018
Therapeutic inflammatory monocyte modulation using immune-modifying microparticles
Daniel R Getts1, Rachael L Terry, Meghann Teague Getts
1The Discipline of Pathology, School of Medical Sciences, Bosch Institute, Sydney Medical School, University of Sydney, Sydney, New South Wales 2006, Australia.
Abstract:
Inflammatory monocyte-derived effector cells play an important role in the pathogenesis of numerous inflammatory diseases. However, no treatment option exists that is capable of modulating these cells specifically. We show that infused negatively charged, immune-modifying microparticles (IMPs), derived from polystyrene, microdiamonds, or biodegradable poly(lactic-co-glycolic) acid, were taken up by inflammatory monocytes, in an opsonin-independent fashion, via the macrophage receptor with collagenous structure (MARCO). Subsequently, these monocytes no longer trafficked to sites of inflammation; rather, IMP infusion caused their sequestration in the spleen through apoptotic cell clearance mechanisms and, ultimately, caspase-3-mediated apoptosis. Administration of IMPs in mouse models of myocardial infarction, experimental autoimmune encephalomyelitis, dextran sodium sulfate-induced colitis, thioglycollate-induced peritonitis, and lethal flavivirus encephalitis markedly reduced monocyte accumulation at inflammatory foci, reduced disease symptoms, and promoted tissue repair. Together, these data highlight the intricate interplay between scavenger receptors, the spleen, and inflammatory monocyte function and support the translation of IMPs for therapeutic use in diseases caused or potentiated by inflammatory monocytes.
Insights
Negatively charged microparticles target inflammatory monocytes via MARCO, leading to spleen sequestration and apoptosis. This approach effectively reduces inflammation and disease symptoms in various mouse models.
Area of Science:
- Immunology
- Biomaterials Science
- Pathology
Background:
- Inflammatory monocytes are key drivers in many diseases.
- Current treatments lack specificity for modulating these cells.
- Targeting inflammatory monocytes offers a potential therapeutic strategy.
Purpose of the Study:
- To investigate the therapeutic potential of immune-modifying microparticles (IMPs) for inflammatory diseases.
- To elucidate the mechanism of IMP uptake and action on inflammatory monocytes.
Main Methods:
- Administration of negatively charged IMPs (polystyrene, microdiamonds, PLGA) to mouse models.
- Analysis of monocyte uptake via the MARCO receptor.
- Assessment of monocyte trafficking, spleen sequestration, and apoptosis.
- Evaluation of disease severity and tissue repair in models of myocardial infarction, EAE, colitis, peritonitis, and encephalitis.
Main Results:
- IMPs were efficiently taken up by inflammatory monocytes through MARCO in an opsonin-independent manner.
- IMPs induced monocyte sequestration in the spleen and subsequent caspase-3-mediated apoptosis.
- IMP treatment significantly reduced monocyte accumulation at inflammatory sites across multiple disease models.
- Disease symptoms were ameliorated, and tissue repair was promoted following IMP administration.
Conclusions:
- IMPs effectively modulate inflammatory monocyte function by promoting their clearance.
- This mechanism involves MARCO receptor interaction, spleen sequestration, and apoptosis.
- IMPs demonstrate broad therapeutic potential for inflammatory diseases driven by monocytes.
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