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Thromb Haemost. 2016 Jan;115(2):311-23. doi: 10.1160/TH15-05-0389. Epub 2015 Sep 3.

Platelet microparticles reprogram macrophage gene expression and function.

Author information

1
Dr. Patrick Provost, CHUQ Research Center/CHUL, 2705 Blvd Laurier, Room T1-65, Quebec, QC G1V 4G2, Canada, Tel.: +1 418 525 4444 (ext. 48842), E-mail: patrick.provost@crchudequebec.ulaval.ca.

Abstract

Platelet microparticles (MPs) represent the most abundant MPs subtype in the circulation, and can mediate intercellular communication through delivery of bioactives molecules, such as cytokines, proteins, lipids and RNAs. Here, we show that platelet MPs can be internalised by primary human macrophages and deliver functional miR-126-3p. The increase in macrophage miR-126-3p levels was not prevented by actinomycin D, suggesting that it was not due to de novo gene transcription. Platelet MPs dose-dependently downregulated expression of four predicted mRNA targets of miR-126-3p, two of which were confirmed also at the protein level. The mRNA downregulatory effects of platelet MPs were abrogated by expression of a neutralising miR-126-3p sponge, implying the involvement of miR-126-3p. Transcriptome-wide, microarray analyses revealed that as many as 66 microRNAs and 653 additional RNAs were significantly and differentially expressed in macrophages upon exposure to platelet MPs. More specifically, platelet MPs induced an upregulation of 34 microRNAs and a concomitant downregulation of 367 RNAs, including mRNAs encoding for cytokines/chemokines CCL4, CSF1 and TNF. These changes were associated with reduced CCL4, CSF1 and TNF cytokine/chemokine release by macrophages, and accompanied by a marked increase in their phagocytic capacity. These findings demonstrate that platelet MPs can modify the transcriptome of macrophages, and reprogram their function towards a phagocytic phenotype.

KEYWORDS:

Platelet; gene regulation; macrophage; microRNA; microparticle

PMID:
26333874
DOI:
10.1160/TH15-05-0389
[Indexed for MEDLINE]

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