Pulmonary sarcoidosis is associated with exosomal vitamin D-binding protein and inflammatory molecules
Autor: | Olof Rådmark, Riitta Lahesmaa, Robert Moulder, Casper J.E. Wahlund, Khaleda Rahman Qazi, Anders Eklund, María José Martínez-Bravo, Susanne Gabrielsson, Ana Lukic, Johan Grunewald |
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Jazyk: | angličtina |
Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Adult Male Proteomics Vitamin D-binding protein Immunology Blotting Western Enzyme-Linked Immunosorbent Assay Exosomes ta3111 Flow cytometry Proinflammatory cytokine 03 medical and health sciences 0302 clinical medicine Western blot Sarcoidosis Pulmonary Tandem Mass Spectrometry medicine Immunology and Allergy Humans ta318 Inflammation medicine.diagnostic_test business.industry Vitamin D-Binding Protein ta1182 Middle Aged medicine.disease Flow Cytometry Microvesicles 030104 developmental biology Bronchoalveolar lavage 030220 oncology & carcinogenesis Biomarker (medicine) Female Sarcoidosis business Bronchoalveolar Lavage Fluid Biomarkers Chromatography Liquid |
Zdroj: | Journal of Allergy and Clinical Immunology. 139(4) |
ISSN: | 0091-6749 |
Popis: | Background Sarcoidosis is an inflammatory granulomatous disorder characterized by accumulation of T H 1-type CD4 + T cells and immune effector cells within affected organs, most frequently the lungs. Exosomes are extracellular vesicles conveying intercellular communication with possible diagnostic and therapeutic applications. Objectives We aimed to provide an understanding of the proinflammatory role of bronchoalveolar lavage fluid (BALF) exosomes in patients with sarcoidosis and to find candidates for disease biomarkers. Methods We performed a mass spectrometric proteomics characterization of BALF exosomes from 15 patients with sarcoidosis and 5 healthy control subjects and verified the most interesting results with flow cytometry, ELISA, and Western blot analyses in an additional 39 patients and 22 control subjects. Results More than 690 proteins were identified in the BALF exosomes, several of which displayed significant upregulation in patients, including inflammation-associated proteins, such as leukotriene A 4 hydrolase. Most of the complement-activating factors were upregulated, whereas the complement regulator CD55 was seen less in patients compared with healthy control subjects. In addition, for the first time, we detected vitamin D–binding protein in BALF exosomes, which was more abundant in patients. To evaluate exosome-associated vitamin D–binding protein as a biomarker for sarcoidosis, we investigated plasma exosomes from 23 patients and 11 healthy control subjects and found significantly higher expression in patients. Conclusion Together, these data contribute to understanding the role of exosomes in lung disease and provide suggestions for highly warranted sarcoidosis biomarkers. Furthermore, the validation of an exosome-associated biomarker in the blood of patients provides novel, and less invasive, opportunities for disease diagnosis. |
Databáze: | OpenAIRE |
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