Platelet microparticles reprogram macrophage gene expression and function

Benoit Laffont; Aurélie Corduan; Matthieu Rousseau; Anne-Claire Duchez; Chan Ho C. Lee; Eric Boilard; Patrick Provost

doi:10.1160/th15-05-0389

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2016; 115(02): 311-323
DOI: 10.1160/th15-05-0389

Cellular Haemostasis and Platelets

Schattauer GmbH

Platelet microparticles reprogram macrophage gene expression and function

Benoit Laffont^#

¹CHUQ Research Center/CHUL, Laurier, Quebec, Quebec, Canada

²Department of Microbiology-Infectiology and Immunology and Faculty of Medicine, Université Laval, Quebec, Quebec, Canada

,

Aurélie Corduan^#

¹CHUQ Research Center/CHUL, Laurier, Quebec, Quebec, Canada

²Department of Microbiology-Infectiology and Immunology and Faculty of Medicine, Université Laval, Quebec, Quebec, Canada

,

Matthieu Rousseau

¹CHUQ Research Center/CHUL, Laurier, Quebec, Quebec, Canada

²Department of Microbiology-Infectiology and Immunology and Faculty of Medicine, Université Laval, Quebec, Quebec, Canada

,

Anne-Claire Duchez

¹CHUQ Research Center/CHUL, Laurier, Quebec, Quebec, Canada

²Department of Microbiology-Infectiology and Immunology and Faculty of Medicine, Université Laval, Quebec, Quebec, Canada

,

Chan Ho C. Lee

¹CHUQ Research Center/CHUL, Laurier, Quebec, Quebec, Canada

²Department of Microbiology-Infectiology and Immunology and Faculty of Medicine, Université Laval, Quebec, Quebec, Canada

,

Eric Boilard

¹CHUQ Research Center/CHUL, Laurier, Quebec, Quebec, Canada

²Department of Microbiology-Infectiology and Immunology and Faculty of Medicine, Université Laval, Quebec, Quebec, Canada

,

Patrick Provost

¹CHUQ Research Center/CHUL, Laurier, Quebec, Quebec, Canada

²Department of Microbiology-Infectiology and Immunology and Faculty of Medicine, Université Laval, Quebec, Quebec, Canada

› Institutsangaben

Abstract

Summary

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.

Supplementary Material to this article is available online at www.thrombosis-online.com.

Keywords

Platelet - microparticle - macrophage - microRNA - gene regulation

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Referenzen

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