Document Detail


Proinflammatory exosomes in bronchoalveolar lavage fluid of patients with sarcoidosis.
MedLine Citation:
PMID:  20880880     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Sarcoidosis is a systemic disease of unknown aetiology characterised by granuloma formation and the presence of interferon γ (IFNγ)-producing T cells that cause inflammation and tissue damage in multiple organs, especially the lung. Exosomes are nano-sized immunomodulatory vesicles of endosomal origin released from a diverse range of cells and are also found in physiological fluids including bronchoalveolar lavage fluid (BALF) from healthy individuals.
OBJECTIVE: To investigate whether exosomes are enriched in the lungs of patients with sarcoidosis compared with healthy individuals and whether they could contribute to pathogenesis.
DESIGN: BALF exosomes from patients with sarcoidosis (n=36) and healthy controls (n=14) were compared by electron microscopy, flow cytometry, western blot analysis and mass spectrometry. BALF exosomes were incubated with autologous peripheral blood mononuclear cells (PBMCs) or the human bronchial epithelial cell line 16HBE14o-. Cytokines were measured by ELISPOT and ELISA.
RESULTS: BALF from patients with sarcoidosis showed increased levels of exosomes compared with healthy individuals. Exosomes from patients showed significantly higher expression of MHC class I and II, tetraspanins CD9, CD63 and CD81 as well as neuregulin-1, known to be associated with cancer progression. Furthermore, BALF exosomes from patients induced significantly higher IFNγ and interleukin (IL)-13 production in autologous PBMCs compared with healthy individuals and could also stimulate IL-8 production from epithelial cells.
CONCLUSION: The results indicate for the first time a role for exosomes in human lung disease with possible contributions to the initiation and progression of inflammation in sarcoidosis. This suggests that exosomes may be a new potential target for the clinical treatment of lung diseases.
Authors:
Khaleda R Qazi; Patricia Torregrosa Paredes; Benita Dahlberg; Johan Grunewald; Anders Eklund; Susanne Gabrielsson
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-09-29
Journal Detail:
Title:  Thorax     Volume:  65     ISSN:  1468-3296     ISO Abbreviation:  Thorax     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-10-22     Completed Date:  2010-11-23     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0417353     Medline TA:  Thorax     Country:  England    
Other Details:
Languages:  eng     Pagination:  1016-24     Citation Subset:  IM    
Affiliation:
Department of Medicine, Clinical Allergy Research Unit, Karolinska Institutet and University Hospital, Stockholm, Sweden.
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MeSH Terms
Descriptor/Qualifier:
Adult
Bronchoalveolar Lavage Fluid / cytology*
Cell Line
Cells, Cultured
Cytokines / biosynthesis
Epithelial Cells / metabolism
Exosomes / chemistry,  physiology*,  ultrastructure
Female
Humans
Inflammation Mediators / metabolism
Interleukin-8 / biosynthesis
Leukocytes, Mononuclear / metabolism
Male
Middle Aged
Proteins / analysis
Sarcoidosis, Pulmonary / metabolism,  pathology*
Young Adult
Chemical
Reg. No./Substance:
0/Cytokines; 0/Inflammation Mediators; 0/Interleukin-8; 0/Proteins
Comments/Corrections
Comment In:
Thorax. 2010 Nov;65(11):947-8   [PMID:  20937642 ]

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