Abstract
Intercellular communication via extracellular vesicles (EVs) and their target cells, especially immune cells, results in functional and phenotype changes that consequently may play a significant role in various physiological states and the pathogenesis of immune-mediated disorders. Monocytes are the most prominent environment-sensing immune cells in circulation, skilled to shape their microenvironments via cytokine secretion and further differentiation. Both the circulating monocyte subset distribution and the blood plasma EV pattern are characteristic for preeclampsia, a pregnancy induced immune-mediated hypertensive disorder. We hypothesized that preeclampsia-associated EVs (PE-EVs) induced functional and phenotypic alterations of monocytes. First, we proved EV binding and uptake by THP-1 cells. Cellular origin and protein cargo of circulating PE-EVs were characterized by flow cytometry and mass spectrometry. An altered phagocytosis-associated molecular pattern was found on 12.5 K fraction of PE-EVs: an elevated CD47 “don’t eat me” signal (p < 0.01) and decreased exofacial phosphatidylserine “eat-me” signal (p < 0.001) were found along with decreased uptake of these PE-EVs (p < 0.05). The 12.5 K fraction of PE-EVs induced significantly lower chemotaxis (p < 0.01) and cell motility but accelerated cell adhesion of THP-1 cells (p < 0.05). The 12.5 K fraction of PE-EVs induced altered monocyte functions suggest that circulating EVs may have a role in the pathogenesis of preeclampsia.
Highlights
Intercellular communication via extracellular vesicles (EVs) and their target cells, especially immune cells, results in functional and phenotype changes that may play a significant role in various physiological states and the pathogenesis of immune-mediated disorders
Circulating EVs were positive for CD63 (mean ± SEM: healthy pregnant- derived EVs (HP-EVs) = 3461 ± 715 preeclampsia-associated EVs (PE-EVs) = 12778 ± 4698 p = 0.067 (n = 13) Suppl
Immunophenotyping of circulating EVs revealed that most detected EVs were derived from platelets and their number was decreased in preeclamptic samples (26 622 ± 4 173 EVs/μL) compared to healthy pregnant- derived EVs (HP-EVs) (60 184 ± 5 504 EVs/μL)
Summary
Intercellular communication via extracellular vesicles (EVs) and their target cells, especially immune cells, results in functional and phenotype changes that may play a significant role in various physiological states and the pathogenesis of immune-mediated disorders. Monocytes are the most prominent environment-sensing immune cells in circulation, skilled to shape their microenvironments via cytokine secretion and further differentiation Both the circulating monocyte subset distribution and the blood plasma EV pattern are characteristic for preeclampsia, a pregnancy induced immune-mediated hypertensive disorder. The 12.5 K fraction of PE-EVs induced altered monocyte functions suggest that circulating EVs may have a role in the pathogenesis of preeclampsia. Circulating monocytes are one of the most prominent environment- monitoring and sensing immune cells characterized by high plasticity, tissue infiltration capacity and cytokine production[25] They have remarkable multipotency, and can differentiate into either inflammatory or anti-inflammatory subsets based on the surrounding stimuli[26]. Preeclampsia is a pregnancy-specific, immune-mediated inflammatory hypertensive disorder, characterized by altered circulating monocyte subsets[27]. The causes of the detected inflammatory reaction in both healthy and preeclamptic pregnancies are still unknown[20]
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