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Pei Cui, Haiming Xin, Yongming Yao, Shichu Xiao, Feng Zhu, Zhenyu Gong, Zhiping Tang, Qiu Zhan, Wei Qin, Yanhua Lai, Xiaohui Li, Yalin Tong, Zhaofan Xia
BACKGROUND: White smoke inhalation (WSI) is an uncommon but potentially deadly cause of acute lung injury and acute respiratory distress syndrome for which no effective pharmaceutical treatment has been developed. This study aimed to determine the protective effects of human amnion-derived mesenchymal stem cells (hAMSCs) against WSI-induced lung injury in rats. METHODS: hAMSCs were injected into rats via the tail vein 4 h after WSI. At 1, 3, 7, 14, and 28 days after cell injection, hAMSCs labeled with PKH26 in lung, heart, liver, and kidney tissues were observed by fluorescence microscopy...
April 12, 2018: Stem Cell Research & Therapy
Nagaraja Nagre, Shaohua Wang, Thomas Kellett, Ragu Kanagasabai, Jing Deng, Miyuki Nishi, Konstantin Shilo, Richard A Oeckler, Jack C Yalowich, Hiroshi Takeshima, John Christman, Rolf D Hubmayr, Xiaoli Zhao
Alveolar epithelial and endothelial cell injury is a major feature of the acute respiratory distress syndrome, in particular when in conjunction with ventilation therapies. Previously we showed [Kim SC, Kellett T, Wang S, Nishi M, Nagre N, Zhou B, Flodby P, Shilo K, Ghadiali SN, Takeshima H, Hubmayr RD, Zhao X. Am J Physiol Lung Cell Mol Physiol 307: L449-L459, 2014.] that tripartite motif protein 72 (TRIM72) is essential for amending alveolar epithelial cell injury. Here, we posit that TRIM72 improves cellular integrity through its interaction with caveolin 1 (Cav1)...
March 1, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
John T Li, Andrew C Melton, George Su, David E Hamm, Michael LaFemina, James Howard, Xiaohui Fang, Sudarshan Bhat, Kieu-My Huynh, Cecilia M O'Kane, Rebecca J Ingram, Roshell R Muir, Daniel F McAuley, Michael A Matthay, Dean Sheppard
Acute respiratory distress syndrome (ARDS) is a devastating disorder characterized by increased alveolar permeability with no effective treatment beyond supportive care. Current mechanisms underlying ARDS focus on alveolar endothelial and epithelial injury caused by products of innate immune cells and platelets. However, the role of adaptive immune cells in ARDS remains largely unknown. In this study, we report that expansion of Ag-specific αβTh17 cells contributes to ARDS by local secretion of IL-17A, which in turn directly increases alveolar epithelial permeability...
July 1, 2015: Journal of Immunology: Official Journal of the American Association of Immunologists
James Walter, Lorraine B Ware, Michael A Matthay
Multipotent mesenchymal stem (stromal) cells (MSCs) have shown promising therapeutic effects in preclinical models of both acute respiratory distress syndrome (ARDS) and sepsis. Although initial research focused on the ability of MSCs to engraft at sites of tissue injury, increasing evidence suggests that MSCs have their therapeutic effects through mechanisms unrelated to long-term incorporation into host tissue. One of the most compelling of these pathways is the ability of MSCs to interact with injured tissue through the release of soluble bioactive factors...
December 2014: Lancet Respiratory Medicine
David Machado-Aranda, Krishnan Raghavendran
Several of the biological processes involved in the pathogenesis of acute lung injury and acute respiratory distress syndrome after lung contusion are regulated at a genetic and epigenetic level. Thus, strategies to manipulate gene expression in this context are highly desirable not only to elucidate the mechanisms involved but also to look for potential therapies. In the present chapter, we describe mouse and rat models of inducing blunt thoracic injury followed by electroporation-mediated gene delivery to the lung...
2014: Methods in Molecular Biology
Charles A Downs, David Q Trac, Lisa H Kreiner, Amity F Eaton, Nicholle M Johnson, Lou Ann Brown, My N Helms
Chronic alcohol consumption is associated with increased incidence of ICU-related morbidity and mortality, primarily from acute respiratory distress syndrome (ARDS). However, the mechanisms involved are unknown. One explanation is that alcohol regulates epithelial sodium channels (ENaC) via oxidant signaling to promote a pro- injury environment. We used small rodent models to mimic acute and chronic alcohol consumption and tested the hypothesis that ethanol (EtOH) would affect lung fluid clearance by up-regulating ENaC activity in the lung...
2013: PloS One
Yun Shi, Bo Zhang, Xiang-Jun Chen, Dun-Quan Xu, Yan-Xia Wang, Hai-Ying Dong, Shi-Rong Ma, Ri-He Sun, Yan-Ping Hui, Zhi-Chao Li
The renin-angiotensin-aldosterone system (RAAS) plays an important role in the pathogenesis of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Angiotensin converting enzyme 2 (ACE2) plays a protective role in acute lung injury. Osthole, a natural coumarin derivative extracted from traditional Chinese medicines, is known to have anti-inflammatory effect, but the effect of osthole on the ALI is largely unknown. The aim of this study is to explore whether and by what mechanisms osthole protects lipopolysaccharide(LPS)-induced acute lung injury...
March 12, 2013: European Journal of Pharmaceutical Sciences
Akihiko Ichikawa, Keiji Kuba, Masayuki Morita, Shinsuke Chida, Hiroyuki Tezuka, Hiromitsu Hara, Takehiko Sasaki, Toshiaki Ohteki, V Marco Ranieri, Claudia C dos Santos, Yoshihiro Kawaoka, Shizuo Akira, Andrew D Luster, Bao Lu, Josef M Penninger, Stefan Uhlig, Arthur S Slutsky, Yumiko Imai
RATIONALE: Patients who developed acute respiratory distress syndrome (ARDS) after infection with severe respiratory viruses (e.g., severe acute respiratory syndrome-coronavirus, H5N1 avian influenza virus), exhibited unusually high levels of CXCL10, which belongs to the non-ELR (glutamic-leucine-arginine) CXC chemokine superfamily. CXCL10 may not be a bystander to the severe virus infection but may directly contribute to the pathogenesis of neutrophil-mediated, excessive pulmonary inflammation...
January 1, 2013: American Journal of Respiratory and Critical Care Medicine
Stephen Joza, Jinxia Wang, Emily Fox, Valerie Hillman, Cameron Ackerley, Martin Post
Respiratory diseases of the newborn can arise from the disruption of essential angiogenic pathways. Neuropilin-1 (NRP1), which is a critical receptor implicated in systemic vascular growth and remodeling, binds two distinct ligand families: vascular endothelial growth factor (VEGF) and class 3 semaphorins (SEMA3). Although the function of VEGF-NRP1 interactions in vascular development is well described, the importance of SEMA3-NRP1 signaling in systemic or pulmonary vascular morphogenesis is debated. We sought to characterize the effect of deficient SEMA3-NRP1 signaling on fetal pulmonary vascular development in a mouse model...
December 2012: American Journal of Pathology
Badreddine Fehri, Jean-Marc Aiache, Kk Mueen Ahmed
BACKGROUND: Globularia alypum L. (Globulariaceae) is a shrub growing in the Mediterranean basin and known to be used as a popular medicine for its several pharmacological properties against rheumatism, gout, typhoid, intermittent fever, and diabetes. MATERIALS AND METHODS: The acute and chronic toxicities of a G. alypum L. aqueous leaf extract were studied in animals. Acute toxicity was performed in male and female mice whereas chronic toxicity was realized in male and female rats that orally received the drug at the doses of 300 and 600 mg/kg/24 h for 30 days...
July 2012: Pharmacognosy Research
Madathilparambil V Suresh, Bi Yu, David Machado-Aranda, Matthew D Bender, Laura Ochoa-Frongia, Jadwiga D Helinski, Bruce A Davidson, Paul R Knight, Cory M Hogaboam, Bethany B Moore, Krishnan Raghavendran
Lung contusion (LC), commonly observed in patients with thoracic trauma is a leading risk factor for development of acute lung injury/acute respiratory distress syndrome. Previously, we have shown that CC chemokine ligand (CCL)-2, a monotactic chemokine abundant in the lungs, is significantly elevated in LC. This study investigated the nature of protection afforded by CCL-2 in acute lung injury/acute respiratory distress syndrome during LC, using rats and CC chemokine receptor (CCR) 2 knockout (CCR2(-/-)) mice...
June 2012: American Journal of Respiratory Cell and Molecular Biology
Laura Dada, Angel R Gonzalez, Daniela Urich, Saul Soberanes, Tomas S Manghi, Sergio E Chiarella, Navdeep S Chandel, G R Scott Budinger, Gökhan M Mutlu
OBJECTIVE: Alcohol intake increases the risk of acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) and is associated with poor outcomes in patients who develop these syndromes. No specific therapies are currently available to treat or decrease the risk of ARDS in patients with alcoholism. We have recently shown increased levels of lung adenosine inhibit alveolar fluid clearance, an important predictor of outcome in patients with ARDS. We hypothesized that alcohol might worsen lung injury by increasing lung adenosine levels, resulting in impaired active Na(+) transport in the lung...
2012: PloS One
Gabriella Aschkenasy, Zohar Bromberg, Nichelle Raj, Clifford S Deutschman, Yoram G Weiss
The Acute respiratory distress syndrome (ARDS) is a highly lethal inflammatory lung disorder. Apoptosis plays a key role in its pathogenesis. We showed that an adenovirus expressing the 70 kDa heat shock protein Hsp70 (AdHSP) protected against sepsis-induced lung injury. In this study we tested the hypothesis that AdHSP attenuates apoptosis in sepsis-induced lung injury. Sepsis was induced in rats via cecal ligation and double puncture (2CLP). At the time of 2CLP PBS, AdHSP or AdGFP (an adenoviral vector expressing green fluorescent protein) were injected into the tracheas of septic rats...
2011: PloS One
Pooja A Kumar, Yuanyu Hu, Yusuke Yamamoto, Neo Boon Hoe, Tay Seok Wei, Dakai Mu, Yan Sun, Lim Siew Joo, Rania Dagher, Elisabeth M Zielonka, De Yun Wang, Bing Lim, Vincent T Chow, Christopher P Crum, Wa Xian, Frank McKeon
The extent of lung regeneration following catastrophic damage and the potential role of adult stem cells in such a process remains obscure. Sublethal infection of mice with an H1N1 influenza virus related to that of the 1918 pandemic triggers massive airway damage followed by apparent regeneration. We show here that p63-expressing stem cells in the bronchiolar epithelium undergo rapid proliferation after infection and radiate to interbronchiolar regions of alveolar ablation. Once there, these cells assemble into discrete, Krt5+ pods and initiate expression of markers typical of alveoli...
October 28, 2011: Cell
Anja H Hergrueter, Khoi Nguyen, Caroline A Owen
No abstract text is available yet for this article.
April 2011: American Journal of Physiology. Lung Cellular and Molecular Physiology
Arun Kumar, Mark Glaum, Nagwa El-Badri, Shyam Mohapatra, Edward Haller, Seungjoo Park, Leslie Patrick, Leigh Nattkemper, Dawn Vo, Don F Cameron
Using current methodologies, drug delivery to small airways, terminal bronchioles, and alveoli (deep lung) is inefficient, especially to the lower lungs. Urgent lung pathologies such as acute respiratory distress syndrome (ARDS) and post-lung transplantation complications are difficult to treat, in part due to the methodological limitations in targeting the deep lung with high efficiency drug distribution to the site of pathology. To overcome drug delivery limitations inhibiting the optimization of deep lung therapy, isolated rat Sertoli cells preloaded with chitosan nanoparticles were use to obtain a high-density distribution and concentration (92%) of the nanoparticles in the lungs of mice by way of the peripheral venous vasculature rather than the more commonly used pulmonary route...
2011: Cell Transplantation
G R Scott Budinger, Gökhan M Mutlu, Daniela Urich, Saul Soberanes, Leonard J Buccellato, Keenan Hawkins, Sergio E Chiarella, Kathryn A Radigan, James Eisenbart, Hemant Agrawal, Sara Berkelhamer, Siegfried Hekimi, Jianke Zhang, Harris Perlman, Paul T Schumacker, Manu Jain, Navdeep S Chandel
RATIONALE: Acute lung injury and the acute respiratory distress syndrome are characterized by increased lung oxidant stress and apoptotic cell death. The contribution of epithelial cell apoptosis to the development of lung injury is unknown. OBJECTIVES: To determine whether oxidant-mediated activation of the intrinsic or extrinsic apoptotic pathway contributes to the development of acute lung injury. METHODS: Exposure of tissue-specific or global knockout mice or cells lacking critical components of the apoptotic pathway to hyperoxia, a well-established mouse model of oxidant-induced lung injury, for measurement of cell death, lung injury, and survival...
April 15, 2011: American Journal of Respiratory and Critical Care Medicine
Ali Akram, Bing Han, Hussain Masoom, Claudia Peng, Emily Lam, Michael L Litvack, Xiaohui Bai, Yuexin Shan, Tsonwin Hai, Jane Batt, Arthur S Slutsky, Haibo Zhang, Wolfgang M Kuebler, Jack J Haitsma, Mingyao Liu, Claudia C dos Santos
RATIONALE: Ventilator-induced lung injury (VILI) significantly contributes to mortality in patients with acute respiratory distress syndrome, the most severe form of acute lung injury. Understanding the molecular basis for response to cyclic stretch (CS) and its derangement during high-volume ventilation is of high priority. OBJECTIVES: To identify specific molecular regulators involved in the development of VILI. METHODS: We undertook a comparative examination of cis-regulatory sequences involved in the coordinated expression of CS-responsive genes using microarray analysis...
August 15, 2010: American Journal of Respiratory and Critical Care Medicine
Alexandra Hicks, Robert Goodnow, Gary Cavallo, Shahid A Tannu, Jessica D Ventre, Danielle Lavelle, Jose M Lora, John Satjawatcharaphong, Martin Brovarney, Karim Dabbagh, Nadine S Tare, Hyesun Oh, Martin Lamb, Achyutharao Sidduri, Romyr Dominique, Qi Qiao, Jian Ping Lou, Paul Gillespie, Nader Fotouhi, Agnieszka Kowalczyk, Grazyna Kurylko, Rachid Hamid, Matthew B Wright, Anjula Pamidimukkala, Thomas Egan, Ueli Gubler, Ann F Hoffman, Xin Wei, Ying L Li, John O'Neil, Ruben Marcano, Karen Pozzani, Tina Molinaro, Jennifer Santiago, Laura Singer, Maureen Hargaden, David Moore, A Robert Catala, Lisa C F Chao, Janet Benson, Thomas March, Radhika Venkat, Helena Mancebo, Louis M Renzetti
Asthma, chronic obstructive pulmonary disease (COPD) and acute lung injury/acute respiratory distress syndrome (ALI/ARDS) are characterized by neutrophilic inflammation and elevated levels of leukotriene B4 (LTB4). However, the exact role of LTB4 pathways in mediating pulmonary neutrophilia and the potential therapeutic application of LTB4 receptor antagonists in these diseases remains controversial. Here we show that a novel dual BLT1 and BLT2 receptor antagonist, RO5101576, potently inhibited LTB4-evoked calcium mobilization in HL-60 cells and chemotaxis of human neutrophils...
June 2010: Prostaglandins & Other Lipid Mediators
Koji Kuronuma, Hiroaki Mitsuzawa, Katsuyuki Takeda, Chiaki Nishitani, Edward D Chan, Yoshio Kuroki, Mari Nakamura, Dennis R Voelker
Lipopolysaccharide (LPS), derived from Gram-negative bacteria, is a major cause of acute lung injury and respiratory distress syndrome. Pulmonary surfactant is secreted as a complex mixture of lipids and proteins onto the alveolar surface of the lung. Surfactant phospholipids are essential in reducing surface tension at the air-liquid interface and preventing alveolar collapse at the end of the respiratory cycle. In the present study, we determined that palmitoyl-oleoyl-phosphatidylglycerol and phosphatidylinositol, which are minor components of pulmonary surfactant, and synthetic dimyristoylphosphatidylglycerol regulated the inflammatory response of alveolar macrophages...
September 18, 2009: Journal of Biological Chemistry
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