Granulocyte-derived extracellular vesicles activate monocytes and are associated with mortality in intensive care unit patients

Ali Danesh, Heather C. Inglis, Mohamed Abdel-Mohsen, Xutao Deng, Avril Adelman, Kenneth B. Schechtman, John W. Heitman, Ryan Vilardi, Avani Shah, Sheila M. Keating, Mitchell J. Cohen, Evan S. Jacobs, Satish K. Pillai, Jacques Lacroix, Philip C. Spinella, Philip J. Norris

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

To understand how extracellular vesicle (EV) subtypes differentially activate monocytes, a series of in vitro studies were performed. We found that plasma-EVs biased monocytes toward an M1 profile. Culturing monocytes with granulocyte-, monocyte-, and endothelial-EVs induced several pro-inflammatory cytokines. By contrast, platelet-EVs induced TGF-β and GM-CSF, and red blood cell (RBC)-EVs did not activate monocytes in vitro. The scavenger receptor CD36 was important for binding of RBC-EVs to monocytes, while blockade of CD36, CD163, CD206, TLR1, TLR2, and TLR4 did not affect binding of plasma-EVs to monocytes in vitro. To identify mortality risk factors, multiple soluble factors and EV subtypes were measured in patients' plasma at intensive care unit admission. Of 43 coagulation factors and cytokines measured, two were significantly associated with mortality, tissue plasminogen activator and cystatin C. Of 14 cellular markers quantified on EVs, 4 were early predictors of mortality, including the granulocyte marker CD66b. In conclusion, granulocyte-EVs have potent pro-inflammatory effects on monocytes in vitro. Furthermore, correlation of early granulocyte-EV levels with mortality in critically ill patients provides a potential target for intervention in management of the pro-inflammatory cascade associated with critical illness.

Original languageEnglish
Article number956
JournalFrontiers in immunology
Volume9
Issue numberMAY
DOIs
StatePublished - May 8 2018

Keywords

  • Exosomes
  • Extracellular vesicles
  • Granulocytes
  • Intensive care unit
  • Microvesicles
  • Monocytes
  • Mortality
  • Receptor

Fingerprint Dive into the research topics of 'Granulocyte-derived extracellular vesicles activate monocytes and are associated with mortality in intensive care unit patients'. Together they form a unique fingerprint.

  • Cite this

    Danesh, A., Inglis, H. C., Abdel-Mohsen, M., Deng, X., Adelman, A., Schechtman, K. B., Heitman, J. W., Vilardi, R., Shah, A., Keating, S. M., Cohen, M. J., Jacobs, E. S., Pillai, S. K., Lacroix, J., Spinella, P. C., & Norris, P. J. (2018). Granulocyte-derived extracellular vesicles activate monocytes and are associated with mortality in intensive care unit patients. Frontiers in immunology, 9(MAY), [956]. https://doi.org/10.3389/fimmu.2018.00956