A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Quantitative Proteomics of Extracellular Vesicles Released from Human Monocyte-Derived Macrophages upon beta-Glucan Stimulation
Tekijät: Cypryk W, Ohman T, Eskelinen EL, Matikainen S, Nyman TA
Kustantaja: AMER CHEMICAL SOC
Julkaisuvuosi: 2014
Journal: Journal of Proteome Research
Tietokannassa oleva lehden nimi: JOURNAL OF PROTEOME RESEARCH
Lehden akronyymi: J PROTEOME RES
Vuosikerta: 13
Numero: 5
Aloitussivu: 2468
Lopetussivu: 2477
Sivujen määrä: 10
ISSN: 1535-3893
DOI: https://doi.org/10.1021/pr4012552(external)
Tiivistelmä
Fungal infections (mycoses) are common diseases of varying severity that cause problems, especially to immunologically compromised people. Fungi express a variety of pathogen-associated molecular patterns on their surface including beta-glucans, which are important immunostimulatory components of fungal cell walls. During stimulatory conditions of infection and colonization, besides intensive intracellular response, human cells actively communicate on the intercellular level by secreting proteins and other biomolecules with several mechanisms. Vesicular secretion remains one of the most important paths for the proteins to exit the cell. Here, we have used high-throughput quantitative proteomics combined with bioinformatics to characterize and quantify vesicle-mediated protein release from beta-glucan-stimulated human macrophages differentiated in vitro from primary blood monocytes. We show that beta-glucan stimulation induces vesicle-mediated protein secretion. Proteomic study identified 540 distinct proteins from the vesicles, and the identified proteins show a proteomic signature characteristic for their cellular origin. Importantly, we identified several receptors, including cation-dependent mannose-6-phosphate receptor, macrophage scavenger receptor, and P2X7 receptor, that have not been identified from vesicles before. Proteomic data together with detailed pathway and network analysis showed that integrins and their cytoplasmic cargo proteins are highly abundant in extracellular vesicles released upon beta-glucan stimulation. In conclusion, the present data provides a solid basis for further studies on the functional role of vesicular protein secretion upon fungal infection.
Fungal infections (mycoses) are common diseases of varying severity that cause problems, especially to immunologically compromised people. Fungi express a variety of pathogen-associated molecular patterns on their surface including beta-glucans, which are important immunostimulatory components of fungal cell walls. During stimulatory conditions of infection and colonization, besides intensive intracellular response, human cells actively communicate on the intercellular level by secreting proteins and other biomolecules with several mechanisms. Vesicular secretion remains one of the most important paths for the proteins to exit the cell. Here, we have used high-throughput quantitative proteomics combined with bioinformatics to characterize and quantify vesicle-mediated protein release from beta-glucan-stimulated human macrophages differentiated in vitro from primary blood monocytes. We show that beta-glucan stimulation induces vesicle-mediated protein secretion. Proteomic study identified 540 distinct proteins from the vesicles, and the identified proteins show a proteomic signature characteristic for their cellular origin. Importantly, we identified several receptors, including cation-dependent mannose-6-phosphate receptor, macrophage scavenger receptor, and P2X7 receptor, that have not been identified from vesicles before. Proteomic data together with detailed pathway and network analysis showed that integrins and their cytoplasmic cargo proteins are highly abundant in extracellular vesicles released upon beta-glucan stimulation. In conclusion, the present data provides a solid basis for further studies on the functional role of vesicular protein secretion upon fungal infection.