In-depth proteomics analysis of human breast milk-derived extracellular vesicles to reveal their origin and targets in the infant's developing immune system
Van Herwijnen, Martijn; Zonneveld, Marijke; Goerdayal, Soenita; Altelaar, Maarten; Hoen, Esther Nolte't; Garssen, Johan; Redegeld, Frank; Wauben, Marca
(2015) Journal of Extracellular Vesicles, volume 4, pp.
(Article)
Abstract
Introduction: Besides providing nutrition, breast milk delivers important signals that stimulate the infant's developing immune system. It has been postulated that extracellular vesicles (EV) in milk support the instruction and/or development of neonatal immunity. However, little is known about the composition of milk-derived EV, partly due to the difficulty to
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purify EV from other components in milk. Methods: In this study, an extensive LC-MS/MS proteomic analysis was performed, whereby EV were isolated from breast milk of 7 individual donors using our recently established optimized density gradient-based isolation protocol [1]. High-density, non-floating complexes were included to compare the contents of EV to other macromolecular structures in milk. A comprehensive protein network was composed tracing the possible cellular origins of milk-derived EV and the potential targets in the gut. Results: An average of 579 proteins was identified in EV, compared to 205 proteins in the non-floating fraction. Interestingly, EV associated proteins like ANXA5 and Flotillin were exclusively identified in EV, while CD9, CD63 and CD81 were also present in non-floating protein complexes. Additionally, MHC-II was identified in the EV fraction only, suggesting that antigenic epitopes may be delivered via EV released from antigen-presenting cells. Besides MHC-I, the mammary epithelial cell marker beta-1,4-galactosyltransferase (lactose subunit) was identified in the EV fraction only, demonstrating EV of epithelial origin. Furthermore, several adhesion molecules (ICAM-1, CEACAM-1) were associated to EV which could allow EV binding to gut epithelial cells and gut resident immune cells. Summary/conclusion: In-depth proteomic analysis and compilation of an extensive network of EV proteins involved in immunity demonstrates that milk-derived EV originate from multiple cellular sources and have the ability to target various cell types in the gut.
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Keywords: protein, epitope, cell adhesion molecule, lactose, galactosyltransferase, cell marker, carcinoembryonic antigen related cell adhesion molecule 1, human, exosome, breast milk, infant, immune system, society, proteomics, milk, intestine, immunity, breast epithelium cell, antigen presenting cell, immunocompetent cell, cells by body anatomy, epithelium cell, density, density gradient, donor, nutrition
ISSN: 2001-3078
Publisher: Co-Action Publishing
(Peer reviewed)
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