Platelet microparticles reprogram macrophage gene expression and function.
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.
Benoit
B
Laffont
Aurélie
A
Corduan
Matthieu
M
Rousseau
Anne-Claire
AC
Duchez
Chan Ho C
CH
Lee
Eric
E
Boilard
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.
Patrick
P
Provost
D001792:Blood Platelets / Q000378:metabolism*; D054407:Chemokine CCL4 / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003609:Dactinomycin / Q000737:chemistry*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D035683:MicroRNAs / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D010587:Phagocytosis; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D014158:Transcription, Genetic; D059467:Transcriptome; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
C066507:CCL4 protein, human; D054407:Chemokine CCL4; D018925:Chemokines; D016207:Cytokines; C527111:MIRN126 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D003609:Dactinomycin; D016173:Macrophage Colony-Stimulating Factor
Platelet; gene regulation; macrophage; microRNA; microparticle