Macrophage microvesicles induce macrophage differentiation and miR-223 transfer

• Published in: Blood 2013-02, Vol.121 (6), p.984-995
• Main Authors: Ismail, Noura, Wang, Yijie, Dakhlallah, Duaa, Moldovan, Leni, Agarwal, Kitty, Batte, Kara, Shah, Prexy, Wisler, Jon, Eubank, Tim D., Tridandapani, Susheela, Paulaitis, Michael E., Piper, Melissa G., Marsh, Clay B.
• Format: Article
• Language: English
• Subjects: Cell Communication; Cell Differentiation; Cell Line; Cell Line, Tumor; Cell-Derived Microparticles - metabolism; Cells, Cultured; Exosomes - metabolism; Gene Expression Profiling; Granulocyte-Macrophage Colony-Stimulating Factor - pharmacology; Human Umbilical Vein Endothelial Cells - metabolism; Humans; Macrophages - cytology; Macrophages - metabolism; Macrophages - ultrastructure; MicroRNAs - genetics; MicroRNAs - metabolism; Microscopy, Confocal; Microscopy, Electron, Transmission; Monocytes - cytology; Monocytes - metabolism; Monocytes - ultrastructure; Oligonucleotide Array Sequence Analysis; Phagocytes, Granulocytes, and Myelopoiesis; RNA Transport - drug effects
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2011-08-374793

Microvesicles are small membrane-bound particles comprised of exosomes and various-sized extracellular vesicles. These are released by several cell types. Microvesicles have a variety of cellular functions from communication to mediating growth and differentiation. Microvesicles contain proteins and nucleic acids. Previously, we showed that plasma microvesicles contain microRNAs (miRNAs). Based on our previous report, the majority of peripheral blood microvesicles are derived from platelets, while mononuclear phagocytes, including macrophages, are the second most abundant population. Here, we characterized macrophage-derived microvesicles and explored their role in the differentiation of naive monocytes. We also identified the miRNA content of the macrophage-derived microvesicles. We found that RNA molecules contained in the macrophage-derived microvesicles were transported to target cells, including mono cytes, endothelial cells, epithelial cells, and fibroblasts. Furthermore, we found that miR-223 was transported to target cells and was functionally active. Based on our observations, we hypothesize that microvesicles bind to and activate target cells. Furthermore, we find that microvesicles induce the differentiation of macrophages. Thus, defining key components of this response may identify novel targets to regulate host defense and inflammation. •Macrophage-derived microvesicles induced cellular differentiation in naive monocytes.•Macrophage-derived microvesicles shuttle of miRNAs to target cells.