The Role of Exosomes in Bronchoalveloar Lavage from Patients with Acute Respiratory Distress Syndrome
Abstract
:1. Background
2. Methods
2.1. Subjects and BAL Collection
2.2. Exosome Extraction
2.3. Western Blot and Enzyme-linked immunosorbent assay
2.4. Cell Culture with BAL Exosomes
2.5. Statistical Analyses
3. Results
3.1. PF Ratio and BAL Exosomes
3.2. BAL Clinical Significance and Composition
3.3. BAL Exosomes in Immune Response
4. Discussion
5. Conclusions
Author Contributions
Acknowledgments
Conflicts of Interest
References
- Ranieri, V.M.; Rubenfeld, G.D.; Thompson, B.T.; Ferguson, N.D.; Caldwell, E.; Fan, E.; Camporota, L.; Slutsky, A.S. Acute respiratory distress syndrome: The Berlin Definition. Jama 2012, 307, 2526–2533. [Google Scholar] [CrossRef] [PubMed]
- Bellani, G.; Laffey, J.G.; Pham, T.; Fan, E.; Brochard, L.; Esteban, A.; Gattinoni, L.; van Haren, F.; Larsson, A.; McAuley, D.F.; et al. Epidemiology, Patterns of Care, and Mortality for Patients With Acute Respiratory Distress Syndrome in Intensive Care Units in 50 Countries. Jama 2016, 315, 788–800. [Google Scholar] [CrossRef] [PubMed]
- Reiss, L.K.; Uhlig, U.; Uhlig, S. Models and mechanisms of acute lung injury caused by direct insults. Eur. J. Cell. Biol. 2012, 91, 590–601. [Google Scholar] [CrossRef] [PubMed]
- Yanez-Mo, M.; Siljander, P.R.; Andreu, Z.; Zavec, A.B.; Borras, F.E.; Buzas, E.I.; Buzas, K.; Casal, E.; Cappello, F.; Carvalho, J.; et al. Biological properties of extracellular vesicles and their physiological functions. J. Extracell Vesicles 2015, 4, 27066. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kubo, H. Extracellular Vesicles in Lung Disease. Chest 2017, 153, 210–216. [Google Scholar] [CrossRef] [PubMed]
- Terrasini, N.; Lionetti, V. Exosomes in Critical Illness. Crit. Care Med. 2017, 45, 1054–1060. [Google Scholar] [CrossRef] [PubMed]
- Robbins, P.D.; Morelli, A.E. Regulation of immune responses by extracellular vesicles. Nat. Rev. Immunol. 2014, 14, 195–208. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wang, W.; Lotze, M.T. Good things come in small packages: Exosomes, immunity and cancer. Cancer Gene Ther. 2014, 21, 139–141. [Google Scholar] [CrossRef]
- De Toro, J.; Herschlik, L.; Waldner, C.; Mongini, C. Emerging roles of exosomes in normal and pathological conditions: New insights for diagnosis and therapeutic applications. Front. Immunol. 2015, 6, 203. [Google Scholar] [CrossRef]
- Takahashi, T.; Kobayashi, S.; Fujino, N.; Suzuki, T.; Ota, C.; He, M.; Yamada, M.; Suzuki, S.; Yanai, M.; Kurosawa, S.; et al. Increased circulating endothelial microparticles in COPD patients: A potential biomarker for COPD exacerbation susceptibility. Thorax 2012, 67, 1067–1074. [Google Scholar] [CrossRef]
- Kadota, T.; Fujita, Y.; Yoshioka, Y.; Araya, J.; Kuwano, K.; Ochiya, T. Extracellular Vesicles in Chronic Obstructive Pulmonary Disease. Int. J. Mol. Sci. 2016, 17, 1801. [Google Scholar] [CrossRef] [PubMed]
- Lacedonia, D.; Carpagnano, G.E.; Trotta, T.; Palladino, G.P.; Panaro, M.A.; Zoppo, L.D.; Foschino Barbaro, M.P.; Porro, C. Microparticles in sputum of COPD patients: A potential biomarker of the disease? Int. J. Chron. Obstruct. Pulmon. Dis. 2016, 11, 527–533. [Google Scholar] [CrossRef] [PubMed]
- Makiguchi, T.; Yamada, M.; Yoshioka, Y.; Sugiura, H.; Koarai, A.; Chiba, S.; Fujino, N.; Tojo, Y.; Ota, C.; Kubo, H.; et al. Serum extracellular vesicular miR-21-5p is a predictor of the prognosis in idiopathic pulmonary fibrosis. Respir. Res. 2016, 17, 110. [Google Scholar] [CrossRef] [PubMed]
- Monsel, A.; Zhu, Y.G.; Gudapati, V.; Lim, H.; Lee, J.W. Mesenchymal stem cell derived secretome and extracellular vesicles for acute lung injury and other inflammatory lung diseases. Expert Opin. Biol. Ther. 2016, 16, 859–871. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kadota, T.; Yoshioka, Y.; Fujita, Y.; Kuwano, K.; Ochiya, T. Extracellular vesicles in lung cancer-From bench to bedside. Semin. Cell Dev. Biol. 2017, 67, 39–47. [Google Scholar] [CrossRef] [PubMed]
- Wahlund, C.J.E.; Eklund, A.; Grunewald, J.; Gabrielsson, S. Pulmonary Extracellular Vesicles as Mediators of Local and Systemic Inflammation. Front. Cell Dev. Biol. 2017, 5, 39. [Google Scholar] [CrossRef] [PubMed]
- Khalyfa, A.; Zhang, C.; Khalyfa, A.A.; Foster, G.E.; Beaudin, A.E.; Andrade, J.; Hanly, P.J.; Poulin, M.J.; Gozal, D. Effect on Intermittent Hypoxia on Plasma Exosomal Micro RNA Signature and Endothelial Function in Healthy Adults. Sleep 2016, 39, 2077–2090. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- King, H.W.; Michael, M.Z.; Gleadle, J.M. Hypoxic enhancement of exosome release by breast cancer cells. BMC Cancer 2012, 12, 421. [Google Scholar] [CrossRef] [PubMed]
- Moon, H.G.; Cao, Y.; Yang, J.; Lee, J.H.; Choi, H.S.; Jin, Y. Lung epithelial cell-derived extracellular vesicles activate macrophage-mediated inflammatory responses via ROCK1 pathway. Cell Death Dis. 2015, 6, e2016. [Google Scholar] [CrossRef] [PubMed]
- Lee, H.; Zhang, D.; Zhu, Z.; Dela Cruz, C.S.; Jin, Y. Epithelial cell-derived microvesicles activate macrophages and promote inflammation via microvesicle-containing microRNAs. Sci. Rep. 2016, 6, 35250. [Google Scholar] [CrossRef] [Green Version]
- Thery, C.; Ostrowski, M.; Segura, E. Membrane vesicles as conveyors of immune responses. Nat. Rev. Immunol. 2009, 9, 581–593. [Google Scholar] [CrossRef] [PubMed]
- Crescitelli, R.; Lässer, C.; Szabó, T.G.; Kittel, A.; Eldh, M.; Dianzani, I.; Buzás, E.I.; Lötvall, J. Distinct RNA profiles in subpopulations of extracellular vesicles: Apoptotic bodies, microvesicles and exosomes. J. Extracell. Vesicles 2013, 2, 20677. [Google Scholar] [CrossRef] [PubMed]
- Li, Z.Y.; Wu, Y.F.; Xu, X.C.; Zhou, J.S.; Wang, Y.; Shen, H.H.; Chen, Z.H. Autophagy as a Double-Edged Sword in Pulmonary Epithelial Injury: A Review and Perspective. Am. J. Physiol. Lung Cell. Mol. Physiol. 2017, 313, L207–L217. [Google Scholar] [CrossRef] [PubMed]
- Kulshreshtha, A.; Ahmad, T.; Agrawal, A.; Ghosh, B. Proinflammatory role of epithelial cell-derived exosomes in allergic airway inflammation. J. Allergy Clin. Immunol 2013, 131, 1194–1203. [Google Scholar] [CrossRef] [PubMed]
- Qazi, K.R.; Torregrosa Paredes, P.; Dahlberg, B.; Grunewald, J.; Eklund, A.; Gabrielsson, S. Proinflammatory exosomes in bronchoalveolar lavage fluid of patients with sarcoidosis. Thorax 2010, 65, 1016–1024. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Torregrosa Paredes, P.; Esser, J.; Admyre, C.; Nord, M.; Rahman, Q.K.; Lukic, A.; Radmark, O.; Gronneberg, R.; Grunewald, J.; Eklund, A.; et al. Bronchoalveolar lavage fluid exosomes contribute to cytokine and leukotriene production in allergic asthma. Allergy 2012, 67, 911–919. [Google Scholar] [CrossRef] [PubMed]
- Senger, D.R.; Galli, S.J.; Dvorak, A.M.; Perruzzi, C.A.; Harvey, V.S.; Dvorak, H.F. Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science 1983, 219, 983–985. [Google Scholar] [CrossRef] [PubMed]
- Leung, D.W.; Cachianes, G.; Kuang, W.J.; Goeddel, D.V.; Ferrara, N. Vascular endothelial growth factor is a secreted angiogenic mitogen. Science 1989, 246, 1306–1309. [Google Scholar] [CrossRef]
- Kuenen, B.C.; Levi, M.; Meijers, J.C.; Kakkar, A.K.; van Hinsbergh, V.W.; Kostense, P.J.; Pinedo, H.M.; Hoekman, K. Analysis of coagulation cascade and endothelial cell activation during inhibition of vascular endothelial growth factor/vascular endothelial growth factor receptor pathway in cancer patients. Arterioscler. Thromb. Vasc. Biol. 2002, 22, 1500–1505. [Google Scholar] [CrossRef]
- Shi, C.S.; Huang, T.H.; Lin, C.K.; Li, J.M.; Chen, M.H.; Tsai, M.L.; Chang, C.C. VEGF Production by Ly6C+high Monocytes Contributes to Ventilator-Induced Lung Injury. PLoS ONE 2016, 11, e0165317. [Google Scholar] [CrossRef]
- Maretta, M.; Toth, S.; Jonecova, Z.; Kruzliak, P.; Kubatka, P.; Pingorova, S.; Vesela, J. Immunohistochemical expression of MPO, CD163 and VEGF in inflammatory cells in acute respiratory distress syndrome: A case report. Int. J. Clin. Exp. Pathol. 2014, 7, 4539–4544. [Google Scholar] [PubMed]
- Medford, A.R.; Millar, A.B. Vascular endothelial growth factor (VEGF) in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS): Paradox or paradigm? Thorax 2006, 61, 621–626. [Google Scholar] [CrossRef] [PubMed]
Patients Characteristics | n = 158 |
---|---|
Age (years) | 59.5 ± 15.0 |
Sex (male) | 102 (64.6%) |
Infectious etiology | 105 (66.5%) |
Intubation | 147 (93.0%) |
PaO2 (mmHg) | 82.0 ± 21.1 |
FiO2 (%) | 56.2 ± 14.6 |
PF ratio (mmHg) | 156.1 ± 55.4 |
ICU stay (days) | 33.3 ± 42.1 |
28 days mortality | 49 (31%) |
BAL Exosome (μg/mL) | 1569.0 ± 2482.6 |
CD9 (μg/mL) | 0.015 ± 0.016 |
CD81 (μg/mL) | 0.172 ± 0.179 |
CD63 (μg/mL) | 0.137 ± 0.156 |
© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Kim, T.H.; Hong, S.-B.; Lim, C.-M.; Koh, Y.; Jang, E.-y.; Huh, J.W. The Role of Exosomes in Bronchoalveloar Lavage from Patients with Acute Respiratory Distress Syndrome. J. Clin. Med. 2019, 8, 1148. https://doi.org/10.3390/jcm8081148
Kim TH, Hong S-B, Lim C-M, Koh Y, Jang E-y, Huh JW. The Role of Exosomes in Bronchoalveloar Lavage from Patients with Acute Respiratory Distress Syndrome. Journal of Clinical Medicine. 2019; 8(8):1148. https://doi.org/10.3390/jcm8081148
Chicago/Turabian StyleKim, Tae Hoon, Sang-Bum Hong, Chae-Mann Lim, Younsuck Koh, Eun-young Jang, and Jin Won Huh. 2019. "The Role of Exosomes in Bronchoalveloar Lavage from Patients with Acute Respiratory Distress Syndrome" Journal of Clinical Medicine 8, no. 8: 1148. https://doi.org/10.3390/jcm8081148