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

• Published in: iScience Vol. 23; no. 6; p. 101135
• Main Authors: Ding, Wei, Rivera, Olivia C., Kelleher, Shannon L., Soybel, David I.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 26.06.2020; Elsevier
• Subjects: Biological Sciences; Cell Biology; Immune Response; Immunology; Specialized Functions of Cells; Biological Sciences; Immunology; Immune Response; Specialized Functions of Cells; Cell Biology
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2020.101135

Macrophages 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. [Display omitted] •Macrolets, outsized extracellular vesicles, release from LPS-stimulated macrophages•Macrolets are rich in tetraspanin proteins such as CD81, CD63, and CD9•Macrolets capture and internalize E. coli bacteria within acidic compartments•Macrolets kill E. coli by a mechanism associated with production of ROS and superoxide Biological Sciences; Immunology; Immune Response; Cell Biology; Specialized Functions of Cells