Neutrophils produce proinflammatory or anti-inflammatory extracellular vesicles depending on the environmental conditions

J Leukoc Biol. 2021 Apr;109(4):793-806. doi: 10.1002/JLB.3A0320-210R. Epub 2020 Sep 18.

Abstract

Extracellular vesicles (EVs) are important elements of intercellular communication. A plethora of different, occasionally even opposite, physiologic and pathologic effects have been attributed to these vesicles in the last decade. A direct comparison of individual observations is however hampered by the significant differences in the way of elicitation, collection, handling, and storage of the investigated vesicles. In the current work, we carried out a careful comparative study on 3, previously characterized types of EVs produced by neutrophilic granulocytes. We investigated in parallel the modulation of multiple blood-related cells and functions by medium-sized vesicles. We show that EVs released from resting neutrophils exert anti-inflammatory action by reducing production of reactive oxygen species (ROS) and cytokine release from neutrophils. In contrast, vesicles generated upon encounter of neutrophils with opsonized particles rather promote proinflammatory processes as they increase production of ROS and cytokine secretion from neutrophils and activate endothelial cells. EVs released from apoptosing cells were mainly active in promoting coagulation. We thus propose that EVs are "custom made," acquiring selective capacities depending on environmental factors prevailing at the time of their biogenesis.

Keywords: IL-8 secretion; coagulation; endothelial cells; migration; phagocytosis; reactive oxygen species.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Coagulation
  • Extracellular Vesicles / metabolism*
  • Extracellular Vesicles / ultrastructure
  • Female
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Inflammation / pathology*
  • Interleukin-8 / metabolism
  • Male
  • Neutrophils / metabolism*
  • Neutrophils / ultrastructure
  • Proteomics
  • Reactive Oxygen Species / metabolism
  • Young Adult

Substances

  • Interleukin-8
  • Reactive Oxygen Species