Therapeutic inflammatory monocyte modulation using immune-modifying microparticles

Daniel R. Getts*, Rachael L. Terry, Meghann Teague Getts, Celine Deffrasnes, Marcus Müller, Carynvan Vreden, Thomas M. Ashhurst, Belal Chami, Derrick McCarthy, Huiling Wu, Ma Jin, Aaron Martin, Lonnie D. Shae, Paul Witting, Geoffrey Scott Kansas, Joachim Kühn, Wali Hafezi, Iain L. Campbell, David Reilly, Jana SayLouise Brown, Melanie Y. White, Stuart J. Cordwell, Steven J. Chadban, Edward Benjamin Thorp, Shisan Bao, Stephen D Miller, Nicholas J.C. King

*Corresponding author for this work

Research output: Contribution to journalArticle

181 Scopus citations

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.

Original languageEnglish (US)
Article number219ra7
JournalScience translational medicine
Volume6
Issue number219
DOIs
StatePublished - Jan 15 2014

ASJC Scopus subject areas

  • Medicine(all)

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    Getts, D. R., Terry, R. L., Getts, M. T., Deffrasnes, C., Müller, M., Vreden, C., Ashhurst, T. M., Chami, B., McCarthy, D., Wu, H., Jin, M., Martin, A., Shae, L. D., Witting, P., Kansas, G. S., Kühn, J., Hafezi, W., Campbell, I. L., Reilly, D., ... King, N. J. C. (2014). Therapeutic inflammatory monocyte modulation using immune-modifying microparticles. Science translational medicine, 6(219), [219ra7]. https://doi.org/10.1126/scitranslmed.3007563