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Granulocyte-Derived Extracellular Vesicles Activate Monocytes and Are Associated With Mortality in Intensive Care

Ali Danesh1,2, Heather C Inglis1, Mohamed Abdel-Mohsen1,2

  • 1Blood Systems Research Institute, San Francisco, CA, United States.

Frontiers in Immunology
|June 6, 2018
PubMed

Insights

Extracellular vesicle (EV) subtypes differentially activate monocytes, with granulocyte-EVs showing potent pro-inflammatory effects. Early granulocyte-EV levels in critically ill patients predict mortality, suggesting a potential therapeutic target.

Area of Science:

  • Immunology
  • Cell Biology
  • Critical Care Medicine

Background:

  • Extracellular vesicles (EVs) play crucial roles in intercellular communication.
  • Understanding how different EV subtypes influence immune cell function is vital for disease management.

Purpose of the Study:

  • To investigate the differential activation of monocytes by various extracellular vesicle (EV) subtypes.
  • To identify EV subtypes and soluble factors associated with mortality in critically ill patients.

Main Methods:

  • In vitro co-culture of human monocytes with different EV subtypes (plasma, granulocyte, monocyte, endothelial, platelet, RBC-EVs).
  • Measurement of cytokine production and immune cell profiling.
  • Analysis of soluble factors and EV markers in plasma from intensive care unit (ICU) patients.

Main Results:

  • Plasma-EVs promoted an M1 monocyte profile; granulocyte-, monocyte-, and endothelial-EVs induced pro-inflammatory cytokines.
  • Platelet-EVs induced TGF-β and GM-CSF; RBC-EVs showed no monocyte activation.
  • Tissue plasminogen activator, cystatin C, and granulocyte marker CD66b on EVs were associated with ICU patient mortality.

Conclusions:

  • Granulocyte-EVs exhibit potent pro-inflammatory effects on monocytes in vitro.
  • Early detection of granulocyte-EV levels may serve as a predictor of mortality in critical illness.
  • Targeting granulocyte-EVs could offer a novel therapeutic strategy for managing critical illness-associated inflammation.
Keywords:
exosomesextracellular vesiclesgranulocytesintensive care unitmicrovesiclesmonocytesmortalityreceptor

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