Macrolets: Outsized Extracellular Vesicles Released from Lipopolysaccharide-Stimulated Macrophages that Trap and Kill Escherichia coli.

Wei Ding,Olivia C Rivera,Shannon L Kelleher,David I Soybel

doi:10.1016/j.isci.2020.101135

Wei Ding, Olivia C Rivera + Show 2 more

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https://doi.org/10.1016/j.isci.2020.101135

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Abstract

SummaryMacrophages release a variety of extracellular vesicles (EVs). Here we describe a previously unreported class of EVs that are released from macrophages in response to Escherichia coli endotoxin, lipopolysaccharide (LPS), that we have named "macrolets" since they are extruded as large "droplets" released from macrophages. Morphologically, macrolets are anuclear, bounded by a single lipid membrane and structurally dependent on an actin cytoskeleton. Macrolets are enriched in tetraspanins and separable on this basis from their parent macrophages. Macrolets are distinguished from classic exosomes by their larger size (10–30 μm), discoid shape, and the presence of organelles. Macrolets are rich in both interleukin 6 (IL-6) and interleukin 6 receptor (IL-6R),and are capable of trapping and killing E. coli in association with production of reactive oxygen species. Our observations offer insights into the mechanisms by which macrophage activities may be amplified in sites of infection, inflammation, and healing.

Highlights

Macrophages play a pivotal role in the initiation, resolution, and persistence of inflammation (Dalli and Serhan, 2017; Ginhoux and Jung, 2014; Varol et al, 2015)
SUMMARY Macrophages release a variety of extracellular vesicles (EVs)
We describe a previously unreported class of EVs that are released from macrophages in response to Escherichia coli endotoxin, lipopolysaccharide (LPS), that we have named "macrolets" since they are extruded as large "droplets" released from macrophages

Summary

Introduction

Macrophages play a pivotal role in the initiation, resolution, and persistence of inflammation (Dalli and Serhan, 2017; Ginhoux and Jung, 2014; Varol et al, 2015). In response to danger signals such as E. coli endotoxin (lipopolysaccharide, LPS), macrophages lay extracellular traps (Doster et al, 2018; Sharma et al, 2017) and produce extracellular vesicles (EVs) containing a variety bioactive molecules (e.g., proteins, carbohydrates, lipids, and nucleic acids) that can influence local inflammatory responses in tissue and lead to phenotypic change in target cells (Esser et al, 2010; Ismail et al, 2013; O’Neill and Quah, 2008) These observations provide evidence for a wide variety of mechanisms by which macrophages are able to sense changes in their surrounding microenvironment and have their signature functions amplified and coordinated. These findings suggest that larger classes of EVs might be produced by other cell types, including the macrophage

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