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

Wei Ding1, Olivia C Rivera2, Shannon L Kelleher3

  • 1Department of Surgery, Penn State College of Medicine and Milton S. Hershey Medical Center, Room# C4810, H149, 500 University Drive, Hershey, PA 17033, USA.

Iscience
|May 23, 2020
PubMed

Insights

Researchers discovered "macrolets," a new type of extracellular vesicle released by macrophages. These macrolets, larger than exosomes, trap and kill bacteria like E. coli, offering insights into infection and inflammation.

Area of Science:

  • Immunology
  • Cell Biology
  • Microbiology

Background:

  • Macrophages are known to release various extracellular vesicles (EVs).
  • The specific mechanisms by which macrophages amplify their activities during infection and inflammation are not fully understood.

Purpose of the Study:

  • To identify and characterize a novel class of macrophage-derived extracellular vesicles.
  • To investigate the functional role of these newly discovered EVs in response to bacterial endotoxin.

Main Methods:

  • Macrophage stimulation with lipopolysaccharide (LPS) from Escherichia coli.
  • Morphological and biochemical characterization of released EVs using microscopy and biochemical assays.
  • Assessment of macrolet's capacity to trap and kill E. coli and associated reactive oxygen species production.

Main Results:

  • A new class of EVs, termed "macrolets," were identified, released from macrophages stimulated by LPS.
  • Macrolets are large (10-30 μm), anuclear, single-membraned vesicles dependent on actin cytoskeleton, distinct from exosomes.
  • Macrolets are enriched in tetraspanins, interleukin-6 (IL-6), and IL-6 receptor (IL-6R), and can trap and kill E. coli via reactive oxygen species.

Conclusions:

  • Macrolets represent a previously unreported mechanism for macrophages to combat bacterial infections.
  • These findings suggest macrolets play a significant role in amplifying macrophage functions at sites of infection, inflammation, and healing.

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