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Therapeutic Inflammatory Monocyte Modulation Using Immune-Modifying Microparticles
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DOI：10.1126/scitranslmed.3007563.png)
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摘要
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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 sulfateinduced 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.
Keyword:
SCAVENGER RECEPTOR
PERIPHERAL-BLOOD
MARCO
PHOSPHATIDYLSERINE
CONTRIBUTES
MACROPHAGES
RECOGNITION
EXPRESSION
CLEARANCE
PEPTIDES
期刊
IF:
14.6
论文数:
4.9K
被引数:
5.3W
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引用论文
Direct Recognition of Superparamagnetic Nanocrystals by Macrophage Scavenger Receptor SR-AI巨噬细胞清道夫受体sr-ai对超顺磁性纳米晶体的直接识别.png)
ACS NANO
ACS NANOIF16
PREAI
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