title: Therapeutic inflammatory monocyte modulation using immune-modifying microparticles.
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.
authors.affiliation: The Discipline of Pathology, School of Medical Sciences, Bosch Institute, Sydney Medical School, University of Sydney, Sydney, New South Wales 2006, Australia.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Getts
authors.forename: Rachael L
authors.initials: RL
authors.lastname: Terry
authors.forename: Meghann Teague
authors.initials: MT
authors.lastname: Getts
authors.forename: Celine
authors.initials: C
authors.lastname: Deffrasnes
authors.forename: Marcus
authors.initials: M
authors.lastname: Müller
authors.forename: Caryn
authors.initials: C
authors.lastname: van Vreden
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Ashhurst
authors.forename: Belal
authors.initials: B
authors.lastname: Chami
authors.forename: Derrick
authors.initials: D
authors.lastname: McCarthy
authors.forename: Huiling
authors.initials: H
authors.lastname: Wu
authors.forename: Jin
authors.initials: J
authors.lastname: Ma
authors.forename: Aaron
authors.initials: A
authors.lastname: Martin
authors.forename: Lonnie D
authors.initials: LD
authors.lastname: Shae
authors.forename: Paul
authors.initials: P
authors.lastname: Witting
authors.forename: Geoffrey S
authors.initials: GS
authors.lastname: Kansas
authors.forename: Joachim
authors.initials: J
authors.lastname: Kühn
authors.forename: Wali
authors.initials: W
authors.lastname: Hafezi
authors.forename: Iain L
authors.initials: IL
authors.lastname: Campbell
authors.forename: David
authors.initials: D
authors.lastname: Reilly
authors.forename: Jana
authors.initials: J
authors.lastname: Say
authors.forename: Louise
authors.initials: L
authors.lastname: Brown
authors.forename: Melanie Y
authors.initials: MY
authors.lastname: White
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Cordwell
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Chadban
authors.forename: Edward B
authors.initials: EB
authors.lastname: Thorp
authors.forename: Shisan
authors.initials: S
authors.lastname: Bao
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Miller
authors.forename: Nicholas J C
authors.initials: NJ
authors.lastname: King
mesh_terms: D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000473:pathology; D002465:Cell Movement; D002470:Cell Survival; D003092:Colitis / Q000473:pathology / Q000517:prevention & control; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000517:prevention & control; D005260:Female; D007249:Inflammation / Q000276:immunology* / Q000473:pathology*; D015212:Inflammatory Bowel Diseases / Q000473:pathology / Q000517:prevention & control; D007668:Kidney / Q000473:pathology; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008863:Microspheres; D009000:Monocytes / Q000276:immunology*; D009206:Myocardium / Q000473:pathology; D010316:Particle Size; D010537:Peritoneum / Q000473:pathology; D011137:Polystyrenes / Q000737:chemistry; D011971:Receptors, Immunologic / Q000378:metabolism; D015427:Reperfusion Injury / Q000517:prevention & control; D013154:Spleen / Q000473:pathology; D014901:West Nile Fever
chemical_list: C092228:Marco protein, mouse; D011137:Polystyrenes; D011971:Receptors, Immunologic