Human saliva, plasma and breast milk exosomes contain RNA: Uptake by macrophages
Open accessAbstract
BACKGROUND: Exosomes are 30-100 nm membrane vesicles of endocytic origin produced by numerous cells. They can mediate diverse biological functions, including antigen presentation. Exosomes have recently been shown to contain functional RNA, which can be delivered to other cells. Exosomes may thus mediate biological functions either by surface-to-surface interactions with cells, or by the delivery of functional RNA to cells. Our aim was therefore to determine the presence of RNA in exosomes from human saliva, plasma and breast milk and whether these exosomes can be taken up by macrophages. METHOD: Exosomes were purified from human saliva, plasma and breast milk using ultracentrifugation and filtration steps. Exosomes were detected by electron microscopy and examined by flow cytometry. Flow cytometry was performed by capturing the exosomes on anti-MHC class II coated beads, and further stain with anti-CD9, anti-CD63 or anti-CD81. Breast milk exosomes were further analysed for the presence of Hsc70, CD81 and calnexin by Western blot. Total RNA was detected with a Bioanalyzer and mRNA was identified by the synthesis of cDNA using an oligo (dT) primer and analysed with a Bioanalyzer. The uptake of PKH67-labelled saliva and breast milk exosomes by macrophages was examined by measuring fluorescence using flow cytometry and fluorescence microscopy. RESULTS: RNA was detected in exosomes from all three body fluids. A portion of the detected RNA in plasma exosomes was characterised as mRNA. Our result extends the characterisation of exosomes in healthy humans and confirms the presence of RNA in human saliva and plasma exosomes and reports for the first time the presence of RNA in breast milk exosomes. Our results also show that the saliva and breast milk exosomes can be taken up by human macrophages. CONCLUSIONS: Exosomes in saliva, plasma and breast milk all contain RNA, confirming previous findings that exosomes from several sources contain RNA. Furthermore, exosomes are readily taken up by macrophages, supporting the notion that exosomal RNA can be shuttled between cells.
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Exosomes can be released by tumor cells, immune cells, mesenchymal stem cells, and endothelial progenitor cells and are detectable in blood, cerebrospinal fluid, saliva, ascites, and urine.
“Following in-depth investigations revealed that exosomes could be released by tumor cells, immune cells, mesenchymal stem cells, and endothelial progenitor cells and are widely detectable in blood, cerebrospinal fluid, saliva, ascites, and even urine [3].”
From The Therapeutic Potential and Clinical Significance of Exosomes as Carriers of Drug Delivery System (2022) · cites this paper as [3]
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- Authors
- Lässer, C., Seyed Alikhani, V., Ekström, K., Eldh, M., Torregrosa Paredes, P., Bossios, A., Sjöstrand, M., Gabrielsson, S., Lötvall, J., & Valadi, H.
- Affiliations
- University of Gothenburg (SE)
- Karolinska University Hospital (SE)
- Corresponding author
- Lötvall, Jan
- ORCID
- Venue
- Journal of Translational Medicine
- Published
- 2011-01-14
- Volume
- 9
- Issue
- 1
- Pages
- 9-9
- ISSN
- 1479-5876 (ISSN-L)
- PMC
- PMC3033821
- OpenAlex
- W2136601868
- Cited by
- 899
- References
- 31
- Citations by year
- 2026: 23 · 2025: 31 · 2024: 60 · 2023: 65 · 2022: 79 · 2021: 81 · 2020: 91 · 2019: 70 · 2018: 72 · 2017: 79 · 2016: 55 · 2015: 59 · 2014: 59 · 2013: 30 · 2012: 36
- FWCI
- 17.29
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Journal of Translational Medicine (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Gothenburg University Publications Electronic Archive (Gothenburg University) (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Vetenskapsrådet
- Sahlgrenska Universitetssjukhuset
- Uppsala Universitet
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Keywords
- exosomes, exosomal RNA, mRNA, macrophage uptake, plasma exosomes, extracellular vesicles, antigen presentation, CD81, CD63, CD9, Hsc70, calnexin, intercellular RNA transfer
- MeSH terms
- Humans, Macrophages, Milk, Human, Plasma, RNA, Saliva, Antigens, CD, Calnexin, HSC70 Heat-Shock Proteins, Exosomes, Tetraspanin 28
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