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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 J+Transl+Med
2016 ; 14
(1
): 181
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Exosomes in the nose induce immune cell trafficking and harbour an altered
protein cargo in chronic airway inflammation
#MMPMID27320496
Lässer C
; O'Neil SE
; Shelke GV
; Sihlbom C
; Hansson SF
; Gho YS
; Lundbäck B
; Lötvall J
J Transl Med
2016[Jun]; 14
(1
): 181
PMID27320496
show ga
BACKGROUND: Exosomes are nano-sized extracellular vesicles participating in
cell-to-cell communication both in health and disease. However, the knowledge
about the functions and molecular composition of exosomes in the upper airways is
limited. The aim of the current study was therefore to determine whether nasal
exosomes can influence inflammatory cells and to establish the proteome of nasal
lavage fluid-derived exosomes in healthy subjects, as well as its alterations in
individuals with chronic airway inflammatory diseases [asthma and chronic
rhinosinusitis (CRS)]. METHODS: Nasal lavage fluid was collected from 14 healthy
subjects, 15 subjects with asthma and 13 subjects with asthma/CRS. Exosomes were
isolated with differential centrifugation and the proteome was analysed by
LC-MS/MS with the application of two exclusion lists as well as using
quantitative proteomics. Ingenuity Pathways Analysis and GO Term finder was used
to predict the functions associated with the exosomal proteome and a migration
assay was used to analyse the effect on immune cells by nasal exosomes. RESULTS:
Firstly, we demonstrate that nasal exosomes can induce migration of several
immune cells, such as monocytes, neutrophils and NK cells in vitro. Secondly, a
mass spectrometry approach, with the application of exclusion lists, was utilised
to generate a comprehensive protein inventory of the exosomes from healthy
subjects. The use of exclusion lists resulted in the identification of ~15 %
additional proteins, and increased the confidence in ~20 % of identified
proteins. In total, 604 proteins were identified in nasal exosomes and the nasal
exosomal proteome showed strong associations with immune-related functions, such
as immune cell trafficking. Thirdly, a quantitative proteomics approach was used
to determine alterations in the exosome proteome as a result of airway
inflammatory disease. Serum-associated proteins and mucins were more abundant in
the exosomes from subjects with respiratory diseases compared to healthy controls
while proteins with antimicrobial functions and barrier-related proteins had
decreased expression. CONCLUSIONS: Nasal exosomes were shown to induce the
migration of innate immune cells, which may be important as the airway epithelium
is the first line of defence against pathogens and allergens. The decreased
expression in barrier and antimicrobial exosomal proteins in subjects with airway
diseases, could possibly contribute to an increased susceptibility to infections,
which have important clinical implications in disease progression.