Modulation of cellular function through immune-activated exosomes

Abstract

Extracellular vesicles classified as exosomes, microvesicles, or apoptotic bodies based on size are shed from most cells under normal as well as pathological conditions. They are released into the surrounding milieu, including plasma, urine, saliva, and tissues. Exosomes are highly enriched in microRNAs (miRs), which function in recipient cells by regulating posttranscriptional processing of targeted genes. Interaction of a miR with its mRNA target typically results in suppression of its gene expression. Peripheral inflammatory conditions can modulate miR expression in immune cells such as circulating monocytes that can influence their migration and differentiation. Changes within monocyte-derived macrophage miR expression can influence exosome content and further affect end-organ target cells.

FIG. 1.

M/Mφ miR arrays. Abundance of miRNAs by microarray performed on isolated normal human monocyte exosomes (bars) (n=3; unpublished data) and published normal human monocyte-derived (n=3; GM-CSF-treated) macrophage exosomes (dots) (Ismail, 2013).

FIG. 2.

Monocyte-derived exosomes are internalized by primary astrocytes and neurons. Primary human monocytes were labeled with Dil C16, exosomes harvested and incubated for 4 h at 37°C on human astrocytes (GFAP) in the top two panels and human neurons (MAP2) in the bottom two panels. Cells were observed by confocal microscopy. Exosomes (red) are observed within the cells. Nuclei were stained with DAPI (blue).