Membrane-coated extracellular vesicles (EVs) released by cells can serve as vehicles
for delivery of biological materials and signals. Recently, we demonstrated that alcohol-treated
hepatocytes cross-talk with immune cells via exosomes containing microRNA (miRNAs).
Here, we hypothesized that alcohol-exposed monocytes can communicate with naive monocytes
via EVs. We observed increased numbers of EVs, mostly exosomes, secreted by primary
human monocytes and THP-1 monocytic cells in the presence of alcohol in a concentration-
and time-dependent manner. EVs derived from alcohol-treated monocytes stimulated naive
monocytes to polarize into M2 macrophages as indicated by increased surface expression
of CD68 (macrophage marker), M2 markers (CD206 (mannose receptor) and CD163 (scavenger
receptor)), secretion of IL-10, and TGF and increased phagocytic activity. miRNA profiling
of the EVs derived from alcohol-treated THP-1 monocytes revealed high expression of
the M2-polarizing miRNA, miR-27a. Treatment of naive monocytes with control EVs overexpressing
miR-27a reproduced the effect of EVs from alcohol-treated monocytes on naive monocytes
and induced M2 polarization, suggesting that the effect of alcohol EVs was mediated
by miR-27a. We found that miR-27a modulated the process of phagocytosis by targeting
CD206 expression on monocytes. Importantly, analysis of circulating EVs from plasma
of alcoholic hepatitis patients revealed increased numbers of EVs that contained high
levels of miR-27a as compared with healthy controls. Our results demonstrate the following:
first, alcohol increases EV production in monocytes; second, alcohol-exposed monocytes
communicate with naive monocytes via EVs; and third, miR-27a cargo in monocyte-derived
EVs can program naive monocytes to polarize into M2 macrophages.
