Extracellular vesicles (EVs) have been implicated in the intercellular transfer of RNA and proteins through cellular secretion into the extracellular space. In blood plasma, circulating EVs are mainly derived from blood cells; however, factors that control plasma EV abundance are largely unknown. Researchers at the University of Southern Denmark estimate the EV secretion rates for blood cell types using reported values for cell-specific plasma EV abundances and their parental cell’s ubiquity in healthy humans. While the researchers found that plasma contains on average ∼2 plasma EVs/cell, the cell-specific EV-to-cell ratio spanned four orders of magnitude from 0.13 ± 0.1 erythrocyte-derived EVs/erythrocyte to (1.9 ± 1.3) × 103 monocyte-derived EVs/monocyte. The steady-state plasma EV level was maintained by an estimated plasma EV secretion rate of (1.5 ± 0.4) × 1012 EVs/min. The cell-specific secretion rate estimates were highest for monocytes (45 ± 21 EVs/cell/min) and lowest for erythrocytes ((3.2 ± 3.0) × 10−3 EVs/cell/min). The estimated basal cell-specific EV secretion rates were not significantly correlated to the cell’s lifespan or size; however, the researchers observed a highly significant correlation to cellular mitochondrial enzyme activities. Together, this analysis indicates that cell-specific mitochondrial metabolism, for example, via reactive oxygen species, affects plasma EV abundance through increased secretion rates, and the results provide a resource for understanding EV function in human health and disease.
Estimation of cell-specific plasma EV to cell ratio
(a) In healthy humans, plasma EVs are mainly derived from blood cells, and ∼41% is derived from the adaptive immune system cells (B, CD4, and CD8 cells), ∼23% from the innate immune system cells (monocytes, NK cells, and neutrophils), and ∼35% from non-immune blood cells (erythrocytes and platelets). The remaining <1% is derived from cells in solid organs. The relative abundances are shown in parentheses. (b) The total number of parental blood cells and their plasma EVs. The overall plasma EV/cell ratio is ∼2. Error bar represents the estimate’s standard deviation. (c) Plasma EV number versus cell abundance for human blood cell types. Error bar represents the estimate’s standard deviation.