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alveolar macrophage extracellular vesicles

Elga Bandeira, Helena Oliveira, Johnatas D Silva, Rubem F S Menna-Barreto, Christina M Takyia, Jung S Suk, Kenneth W Witwer, Michael E Paulaitis, Justin Hanes, Patricia R M Rocco, Marcelo M Morales
BACKGROUND: Silicosis is an occupational disease that affects workers who inhale silica particles, leading to extensive lung fibrosis and ultimately causing respiratory failure. Mesenchymal stromal cells (MSCs) have been shown to exert therapeutic effects in lung diseases and represent an alternative treatment for silicosis. Recently, it has been suggested that similar effects can be achieved by the therapeutic use of extracellular vesicles (EVs) obtained from MSCs. The aim of this study was to investigate the effects of adipose-tissue-derived MSCs (AD-MSCs) or their EVs in a model of silicosis...
May 29, 2018: Respiratory Research
Heedoo Lee, Eric Abston, Duo Zhang, Ashish Rai, Yang Jin
Inflammatory lung responses are one of the characterized features in the pathogenesis of many lung diseases, including acute respiratory distress syndrome (ARDS) and chronic obstructive pulmonary disease (COPD). Alveolar macrophages (AMs) and alveolar epithelial cells are the first line of host defense and innate immunity. Due to their central roles in both the initiation and resolution of inflammatory lung responses, AMs constantly communicate with other lung cells, including the alveolar epithelial cells...
2018: Frontiers in Immunology
So Yoon Ahn, Won Soon Park, Young Eun Kim, Dong Kyung Sung, Se In Sung, Jee Yin Ahn, Yun Sil Chang
We previously reported the role of vascular endothelial growth factor (VEGF) secreted by mesenchymal stem cells (MSCs) in protecting against neonatal hyperoxic lung injuries. Recently, the paracrine protective effect of MSCs was reported to be primarily mediated by extracellular vesicle (EV) secretion. However, the therapeutic efficacy of MSC-derived EVs and the role of the VEGF contained within EVs in neonatal hyperoxic lung injury have not been elucidated. The aim of the study was to determine whether MSC-derived EVs attenuate neonatal hyperoxic lung injury and, if so, whether this protection is mediated via the transfer of VEGF...
April 13, 2018: Experimental & Molecular Medicine
Daniel J Schneider, Jennifer M Speth, Loka R Penke, Scott H Wettlaufer, Joel A Swanson, Marc Peters-Golden
Extracellular vesicles, including exosomes and shed microvesicles (MVs), can be internalized by recipient cells to modulate function. Although the mechanism by which extracellular vesicles are internalized is incompletely characterized, it is generally considered to involve endocytosis and an initial surface-binding event. Furthermore, modulation of uptake by microenvironmental factors is largely unstudied. Here, we used flow cytometry, confocal microscopy, and pharmacologic and molecular targeting to address these gaps in knowledge in a model of pulmonary alveolar cell-cell communication...
December 22, 2017: Journal of Biological Chemistry
Mitsuaki Kojima, Joao A Gimenes-Junior, Theresa W Chan, Brian P Eliceiri, Andrew Baird, Todd W Costantini, Raul Coimbra
Acute lung injury (ALI) is a common cause of morbidity in patients after severe injury due to dysregulated inflammation, which is believed to be driven by gut-derived inflammatory mediators carried via mesenteric lymph (ML). We have previously demonstrated that nano-sized extracellular vesicles, called exosomes, secreted into ML after trauma/hemorrhagic shock (T/HS) have the potential to activate immune cells in vitro Here, we assess the function of ML exosomes in the development of T/HS-induced ALI and the role of TLR4 in the ML exosome-mediated inflammatory response...
January 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Anna Lena Jung, Christina Elena Herkt, Christine Schulz, Kathrin Bolte, Kerstin Seidel, Nicoletta Scheller, Alexandra Sittka-Stark, Wilhelm Bertrams, Bernd Schmeck
Extracellular vesicles from eukaryotic cells and outer membrane vesicles (OMVs) released from gram-negative bacteria have been described as mediators of pathogen-host interaction and intercellular communication. Legionella pneumophila (L. pneumophila) is a causative agent of severe pneumonia. The differential effect of bacterial and host cell vesicles in L. pneumophila infection is unknown so far. We infected THP-1-derived or primary human macrophages with L. pneumophila and isolated supernatant vesicles by differential centrifugation...
July 24, 2017: Scientific Reports
Thomas J Morrison, Megan V Jackson, Erin K Cunningham, Adrien Kissenpfennig, Daniel F McAuley, Cecilia M O'Kane, Anna D Krasnodembskaya
RATIONALE: Acute respiratory distress syndrome (ARDS) remains a major cause of respiratory failure in critically ill patients. Mesenchymal stromal cells (MSCs) are a promising candidate for a cell-based therapy. However, the mechanisms of MSCs' effects in ARDS are not well understood. In this study, we focused on the paracrine effect of MSCs on macrophage polarization and the role of extracellular vesicle (EV)-mediated mitochondrial transfer. OBJECTIVES: To determine the effects of human MSCs on macrophage function in the ARDS environment and to elucidate the mechanisms of these effects...
November 15, 2017: American Journal of Respiratory and Critical Care Medicine
Anna Lena Jung, Kerstin Hoffmann, Christina E Herkt, Christine Schulz, Wilhelm Bertrams, Bernd Schmeck
Bacteria are able to secrete a variety of molecules via various secretory systems. Besides the secretion of molecules into the extracellular space or directly into another cell, Gram-negative bacteria can also form outer membrane vesicles (OMVs). These membrane vesicles can deliver their cargo over long distances, and the cargo is protected from degradation by proteases and nucleases. Legionella pneumophila (L. pneumophila) is an intracellular, Gram-negative pathogen that causes a severe form of pneumonia. In humans, it infects alveolar macrophages, where it blocks lysosomal degradation and forms a specialized replication vacuole...
February 22, 2017: Journal of Visualized Experiments: JoVE
Ziwen Zhu, Duo Zhang, Heedoo Lee, Aravind Ajakumar Menon, Jingxuan Wu, Kebin Hu, Yang Jin
Bacterial pneumonia is a common and serious clinical entity. Alveolar epithelial cells and alveolar macrophages are the first line of defense in the innate immunity against bacterial pathogens. Epithelial cells are known to release chemokines/cytokines that recruit and activate phagocytic cells. However, the signals sent from alveolar macrophages back to the lung epithelial cells remain largely unexplored. We found that LPS, a well-recognized stimulator derived from gram-negative (G- ) bacteria, rapidly and robustly induces the secretion of macrophage-derived extracellular vesicles (EVs)...
June 2017: Journal of Leukocyte Biology
Heedoo Lee, Duo Zhang, Ziwen Zhu, Charles S Dela Cruz, Yang Jin
Intercellular communications between lung epithelial cells and alveolar macrophages play an essential role in host defense against acute lung injury. Hyperoxia-induced oxidative stress is an established model to mimic human lung injury. We show that after hyperoxia-associated oxidative stress, a large amount of extracellular vesicles (EVs) are detectable in bronchoalveolar lavage fluid (BALF) and culture medium of lung epithelial cells. Microvesicles (MVs), but not exosomes (Exos) or apoptotic bodies (Abs), are the main type of EVs found in the early stages after hyperoxia...
October 12, 2016: Scientific Reports
Daniel J Schneider, Jennifer M Speth, Marc Peters-Golden
Unconventional secretion and subsequent uptake of molecular cargo via extracellular vesicles (EVs) is an important mechanism by which cells can exert paracrine effects. While this phenomenon has been widely characterized in the context of their ability to promote inflammation, less is known about the ability of EVs to transfer immunosuppressive cargo. Maintenance of normal physiology in the lung requires suppression of potentially damaging inflammatory responses to the myriad of insults to which it is continually exposed...
2016: Frontiers in Cell and Developmental Biology
H-G Moon, Y Cao, J Yang, J H Lee, H S Choi, Y Jin
Despite decades of research, the pathogenesis of acute respiratory distress syndrome (ARDS) remains poorly understood, thus impeding the development of effective treatment. Diffuse alveolar damage (DAD) and lung epithelial cell death are prominent features of ARDS. Lung epithelial cells are the first line of defense after inhaled stimuli, such as in the case of hyperoxia. We hypothesized that lung epithelial cells release 'messenger' or signaling molecules to adjacent or distant macrophages, thereby initiating or propagating inflammatory responses after noxious insult...
December 10, 2015: Cell Death & Disease
Jaffre J Athman, Ying Wang, David J McDonald, W Henry Boom, Clifford V Harding, Pamela A Wearsch
Mycobacterium tuberculosis is an intracellular pathogen that infects lung macrophages and releases microbial factors that regulate host defense. M. tuberculosis lipoproteins and lipoglycans block phagosome maturation, inhibit class II MHC Ag presentation, and modulate TLR2-dependent cytokine production, but the mechanisms for their release during infection are poorly defined. Furthermore, these molecules are thought to be incorporated into host membranes and released from infected macrophages within exosomes, 40-150-nm extracellular vesicles that derive from multivesicular endosomes...
August 1, 2015: Journal of Immunology: Official Journal of the American Association of Immunologists
You-Sun Kim, Won-Hee Lee, Eun-Jeong Choi, Jun-Pyo Choi, Young Joo Heo, Yong Song Gho, Young-Koo Jee, Yeon-Mok Oh, Yoon-Keun Kim
Recent evidence indicates that Gram-negative bacteria-derived extracellular vesicles (EVs) in indoor dust can evoke neutrophilic pulmonary inflammation, which is a key pathology of chronic obstructive pulmonary disease (COPD). Escherichia coli is a ubiquitous bacterium present in indoor dust and secretes nanometer-sized vesicles into the extracellular milieu. In the current study, we evaluated the role of E. coli-derived EVs on the development of COPD, such as emphysema. E. coli EVs were prepared by sequential ultrafiltration and ultracentrifugation...
April 1, 2015: Journal of Immunology: Official Journal of the American Association of Immunologists
Robin Roychaudhuri, Anja H Hergrueter, Francesca Polverino, Maria E Laucho-Contreras, Kushagra Gupta, Niels Borregaard, Caroline A Owen
A disintegrin and a metalloproteinase domain (ADAM) 9 is known to be expressed by monocytes and macrophages. In this study, we report that ADAM9 is also a product of human and murine polymorphonuclear neutrophils (PMNs). ADAM9 is not synthesized de novo by circulating PMNs. Rather, ADAM9 protein is stored in the gelatinase and specific granules and the secretory vesicles of human PMNs. Unstimulated PMNs express minimal quantities of surface ADAM9, but activation of PMNs with degranulating agonists rapidly (within 15 min) increases PMN surface ADAM9 levels...
September 1, 2014: Journal of Immunology: Official Journal of the American Association of Immunologists
Jens Jäger, Sebastian Marwitz, Jana Tiefenau, Janine Rasch, Olga Shevchuk, Christian Kugler, Torsten Goldmann, Michael Steinert
Histological and clinical investigations describe late stages of Legionnaires' disease but cannot characterize early events of human infection. Cellular or rodent infection models lack the complexity of tissue or have nonhuman backgrounds. Therefore, we developed and applied a novel model for Legionella pneumophila infection comprising living human lung tissue. We stimulated lung explants with L. pneumophila strains and outer membrane vesicles (OMVs) to analyze tissue damage, bacterial replication, and localization as well as the transcriptional response of infected tissue...
January 2014: Infection and Immunity
Y-S Kim, E-J Choi, W-H Lee, S-J Choi, T-Y Roh, J Park, Y-K Jee, Z Zhu, Y-Y Koh, Y S Gho, Y-K Kim
BACKGROUND: Many bacterial components in indoor dust can evoke inflammatory pulmonary diseases. Bacteria secrete nanometre-sized vesicles into the extracellular milieu, but it remains to be determined whether bacteria-derived extracellular vesicles in indoor dust are pathophysiologically related to inflammatory pulmonary diseases. OBJECTIVE: To evaluate whether extracellular vesicles (EV) in indoor air are related to the pathogenesis of pulmonary inflammation and/or asthma...
April 2013: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
Teresa Repasy, Jinhee Lee, Simeone Marino, Nuria Martinez, Denise E Kirschner, Gregory Hendricks, Stephen Baker, Andrew A Wilson, Darrell N Kotton, Hardy Kornfeld
We previously reported that Mycobacterium tuberculosis triggers macrophage necrosis in vitro at a threshold intracellular load of ~25 bacilli. This suggests a model for tuberculosis where bacilli invading lung macrophages at low multiplicity of infection proliferate to burst size and spread to naïve phagocytes for repeated cycles of replication and cytolysis. The current study evaluated that model in vivo, an environment significantly more complex than in vitro culture. In the lungs of mice infected with M...
February 2013: PLoS Pathogens
M-R Kim, S-W Hong, E-B Choi, W-H Lee, Y-S Kim, S G Jeon, M H Jang, Y S Gho, Y-K Kim
BACKGROUND: Recent evidence indicates that Staphylococcus aureus, one of the most important human pathogens, secretes vesicles into the extracellular milieu. OBJECTIVE: To evaluate whether inhalation of S. aureus-derived extracellular vesicles (EV) is causally related to the pathogenesis of inflammatory pulmonary diseases. METHODS: Staphylococcus aureus EV were prepared by sequential ultrafiltration and ultracentrifugation. The innate immune response was evaluated in vitro after the application of EV to airway epithelial cells and alveolar macrophages...
October 2012: Allergy
Motao Zhu, Xin Tian, Xiao Song, Yiye Li, Yanhua Tian, Yuliang Zhao, Guangjun Nie
The mechanisms associated with the induction of systemic immune responses by nanoparticles are not fully understood, but their elucidation is critical to address safety issues associated with the broader medical application of nanotechnology. In this study, a key role of nanoparticle-induced exosomes (extracellularly secreted membrane vesicles) as signaling mediators in the induction of T helper cell type 1 (Th1) immune activation is demonstrated. In vivo exposure to magnetic iron oxide nanoparticles (MIONs) results in significant exosome generation in the alveolar region of Balb/c mice...
September 24, 2012: Small
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