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Mesenchymal Stem Cell Regulation of Macrophage Phagocytosis; Quantitation and Imaging
Published on: July 16, 2021
Platelet microparticles reprogram macrophage gene expression and function
Benoit Laffont, Aurélie Corduan, Matthieu Rousseau
1Dr. Patrick Provost, CHUQ Research Center/CHUL, 2705 Blvd Laurier, Room T1-65, Quebec, QC G1V 4G2, Canada, Tel.: +1 418 525 4444 (ext. 48842),
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.
Insights
Platelet microparticles deliver functional miR-126-3p to macrophages, altering their gene expression and promoting a phagocytic phenotype. This study reveals a novel mechanism of intercellular communication influencing immune cell function.
Area of Science:
- Cell Biology
- Immunology
- Molecular Biology
Background:
- Platelet microparticles (MPs) are abundant in circulation and mediate intercellular communication.
- MPs carry bioactive molecules like cytokines, proteins, lipids, and RNAs.
Purpose of the Study:
- To investigate the internalization of platelet MPs by macrophages.
- To determine the functional consequences of platelet MP delivery of miR-126-3p to macrophages.
Main Methods:
- Primary human macrophages were exposed to platelet MPs.
- Microarray analysis was used to assess global changes in microRNA and RNA expression.
- Functional assays measured cytokine release and phagocytic capacity.
Main Results:
- Platelet MPs were internalized by macrophages, delivering functional miR-126-3p.
- miR-126-3p from platelet MPs downregulated target mRNA and protein expression.
- Platelet MP exposure reprogrammed macrophage transcriptome, upregulating 34 microRNAs and downregulating 367 RNAs.
- Macrophages showed reduced CCL4, CSF1, and TNF release and increased phagocytic capacity.
Conclusions:
- Platelet MPs reprogram macrophage function via miR-126-3p delivery.
- This interaction shifts macrophages towards a phagocytic phenotype.
- Platelet MPs represent a significant mechanism for modulating macrophage immune responses.

