Journal Article

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

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

2018

Overview

To understand how extracellular vesicle (EV) subtypes differentially activate monocytes, a series of 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 . 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 . 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 . 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.

• Publisher: Frontiers Media SA,Frontiers Media S.A
• Subject: Biomarkers - blood / Blood / Blood platelets / CD163 antigen / CD36 antigen / Cell culture / Critical Illness / Cystatin C / Cytokines - immunology / Endocytosis / Erythrocytes / exosomes / Experiments / Extracellular vesicles / Extracellular Vesicles - immunology / Extracellular Vesicles - metabolism / Gene Expression Profiling / Granulocyte-macrophage colony-stimulating factor / Granulocyte-Macrophage Colony-Stimulating Factor - immunology / Granulocytes / Granulocytes - immunology / Granulocytes - metabolism / High-Throughput Nucleotide Sequencing / Hospital Mortality / Humans / Immunology / Inflammation / Intensive care / Intensive Care Units / Leukocytes / Leukocytes (granulocytic) / Macrophages - drug effects / microvesicles / Monocytes / Monocytes - drug effects / Monocytes - immunology / Mortality / Plasma / Risk Factors / Scavenger receptors / t-Plasminogen activator / TLR1 protein / TLR2 protein / TLR4 protein / Toll-like receptors / Transforming Growth Factor beta - immunology / Transforming growth factor-b