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Updated: May 28, 2025

Development and Identification of a Novel Subpopulation of Human Neutrophil-derived Giant Phagocytes In Vitro
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Neutrophil-derived vesicles control complement activation to facilitate inflammation resolution.

Alan Y Hsu1, Qingxiang Huang2, Xiong Pi3

  • 1Department of Pathology, PhD Program in Immunology, Harvard Medical School, Boston, MA 02115, USA; Dana-Farber/Harvard Cancer Center, Boston, MA 02115, USA; Department of Pathology, Mass General Brigham, Boston, MA 02115, USA.

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|February 12, 2025
PubMed
Summary

Neutrophils can resolve inflammation by producing anti-inflammatory extracellular vesicles called LAND-Vs. These vesicles, protected from clearance, use CD55 to reduce inflammation and tissue damage.

Keywords:
CD55COVID-19agingcomplementdo not eat me signalextracellular vesiclesinflammation resolutionlung injuryneutrophilspneumonia

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Area of Science:

  • Immunology
  • Cell Biology
  • Extracellular Vesicles

Background:

  • Neutrophils are primarily known for pro-inflammatory roles and pathogen clearance.
  • Some neutrophil subsets possess immunosuppressive properties, but their mechanisms are not fully understood.

Purpose of the Study:

  • To investigate the potential anti-inflammatory functions of neutrophils beyond pathogen clearance.
  • To characterize novel extracellular vesicles produced by aging neutrophils.

Main Methods:

  • Characterization of large aging-neutrophil-derived vesicles (LAND-Vs) based on size, structure, and biogenesis.
  • Analysis of "do not eat me" signals on LAND-Vs and their interaction with phagocytes.
  • Investigation of CD55's role in LAND-V-mediated anti-inflammatory effects.
  • Identification of lipid raft domains and RhoA-dependent pathways in LAND-V formation.

Main Results:

  • Neutrophils produce unique anti-inflammatory extracellular vesicles (LAND-Vs) that differ from classical vesicle types.
  • LAND-Vs exhibit "do not eat me" signals, evading phagocytosis and accumulating during inflammation resolution.
  • CD55 on LAND-Vs inhibits complement C3 convertase, reducing neutrophil recruitment and tissue damage.
  • LAND-Vs originate from lipid rafts in aging neutrophils via RhoA-dependent budding.

Conclusions:

  • LAND-Vs are novel immunomodulators produced by neutrophils that actively resolve inflammation.
  • CD55-expressing LAND-Vs provide sustained anti-inflammatory effects, mitigating tissue damage.
  • LAND-Vs represent a potential therapeutic target for inflammatory and infectious diseases.