CHOP Deficient Mice Have Augmented Lung Injury with Hyperoxia.

2009 ◽  
Author(s):  
TI Lozon ◽  
WA Altemeier
Keyword(s):  
Lung Injury ◽  
Deficient Mice

Mesenchymal Stromal (stem) Cell (MSC) therapy modulates miR-193b-5p expression to attenuate sepsis-induced acute lung injury

2021 ◽  
pp. 2004216
Author(s):  
Claudia C. dos Santos ◽  
Hajera Amatullah ◽  
Chirag M. Vaswani ◽  
Tatiana Maron-Gutierrez ◽  
Michael Kim ◽  
...  
Keyword(s):  
Stem Cell ◽  
Lung Injury ◽  
Conditioned Media ◽  
Therapeutic Effects ◽  
Host Immune System ◽  
Gene And Protein Expression ◽  
Stromal Stem Cell ◽  
Mesenchymal Stromal Stem Cell ◽  
Deficient Mice

Although mesenchymal stromal (stem) cell (MSC) administration attenuates sepsis-induced lung injury in pre-clinical models, the mechanism(s) of action and host immune system contributions to its therapeutic effects, remain elusive. We show that treatment with MSCs decreased expression of host-derived microRNA (miR)-193b-5p and increased expression of its target gene, the tight junctional protein occludin (Ocln), in lungs from septic mice. Mutating the Ocln 3′ UTR miR-193b-5p binding sequence impaired binding to Ocln mRNA. Inhibition of miR-193b-5p in human primary pulmonary microvascular endothelial cells (HPMECs) prevents tumor necrosis factor (TNF)-induced decrease in Ocln gene and protein expression and loss of barrier function. MSC conditioned media mitigated TNF-induced miR-193b-5p upregulation and Ocln downregulation in vitro. When administered in vivo, MSC conditioned media recapitulated the effects of MSC administration on pulmonary miR-193b-5p and Ocln expression. MiR-193b deficient mice were resistant to pulmonary inflammation and injury induced by LPS instillation. Silencing of Ocln in miR-193b deficient mice partially recovered the susceptibility to LPS-induced lung injury. In vivo inhibition of miR-193b-5p protected mice from endotoxin-induced lung injury. Finally, the clinical significance of these results was supported by the finding of increased miR-193b-5p expression levels in lung autopsy samples from Acute Respiratory Distress Syndrome patients who died with diffuse alveolar damage.

Complement-dependent immune complex-induced bronchial inflammation and hyperreactivity

2001 ◽  
Vol 280 (3) ◽  
pp. L512-L518 ◽  
Author(s):  
Nicholas W. Lukacs ◽  
M. Michael Glovsky ◽  
Peter A. Ward
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Bronchoalveolar Lavage ◽  
Immune Complex ◽  
Airway Hyperreactivity ◽  
Lung Model ◽  
Bronchial Inflammation ◽  
Lung Injury Model ◽  
Airway Responses ◽  
Deficient Mice

Bronchoconstriction responses in the airway are caused by multiple insults and are the hallmark symptom in asthma. In an acute lung injury model in mice, IgG immune complex deposition elicited severe airway hyperreactivity that peaked by 1 h, was maintained at 4 h, and was resolved by 24 h. The depletion of complement with cobra venom factor (CVF) markedly reduced the hyperreactive airway responses, suggesting that complement played an important role in the response. Blockade of C5a with specific antisera also significantly reduced airway hyperreactivity in this acute lung model. Complement depletion by CVF treatment significantly reduced tumor necrosis factor and histamine levels in bronchoalveolar lavage fluids, correlating with reductions in airway hyperreactivity. To further examine the role of specific complement requirement, we initiated the immune complex response in C5-sufficient and C5-deficient congenic animals. The airway hyperreactivity response was partially reduced in the C5-deficient mice. Complement depletion with CVF attenuated airway hyperreactivity in the C5-sufficient mice but had a lesser effect on the airway hyperreactive response and histamine release in bronchoalveolar lavage fluids in C5-deficient mice. These data indicate that acute lung injury in mice after deposition of IgG immune complexes induced airway hyperreactivity that is C5 and C5a dependent.

scholarly journals Fas-deficient mice have impaired alveolar neutrophil recruitment and decreased expression of anti-KC autoantibody:KC complexes in a model of acute lung injury

2012 ◽  
Vol 13 (1) ◽  
pp. 91 ◽  
Author(s):  
Sucheol Gil ◽  
Alex W Farnand ◽  
William A Altemeier ◽  
Sean E Gill ◽  
Anna Kurdowska ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Neutrophil Recruitment ◽  
Deficient Mice

scholarly journals Urokinase Plasminogen Activator Receptor-Deficient Mice Demonstrate Reduced Hyperoxia-Induced Lung Injury

2009 ◽  
Vol 174 (6) ◽  
pp. 2182-2189 ◽  
Author(s):  
Marieke A.D. van Zoelen ◽  
Sandrine Florquin ◽  
Regina de Beer ◽  
Jennie M. Pater ◽  
Marleen I. Verstege ◽  
...  
Keyword(s):  
Lung Injury ◽  
Plasminogen Activator ◽  
Urokinase Plasminogen Activator ◽  
Urokinase Plasminogen Activator Receptor ◽  
Plasminogen Activator Receptor ◽  
Deficient Mice

scholarly journals Ischemia-Reperfusion Lung Injury Is Attenuated in MyD88-Deficient Mice

PLoS ONE ◽  
2013 ◽  
Vol 8 (10) ◽  
pp. e77123 ◽  
Author(s):  
William A. Altemeier ◽  
W. Conrad Liles ◽  
Ana Villagra-Garcia ◽  
Gustavo Matute-Bello ◽  
Robb W. Glenny
Keyword(s):  
Lung Injury ◽  
Ischemia Reperfusion ◽  
Deficient Mice

scholarly journals Caspase-1-Deficient Mice Have Delayed Neutrophil Apoptosis and a Prolonged Inflammatory Response to Lipopolysaccharide-Induced Acute Lung Injury

2002 ◽  
Vol 169 (11) ◽  
pp. 6401-6407 ◽  
Author(s):  
Sarah J. Rowe ◽  
Lucy Allen ◽  
Victoria C. Ridger ◽  
Paul G. Hellewell ◽  
Moira K. B. Whyte
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Response ◽  
Neutrophil Apoptosis ◽  
Caspase 1 ◽  
Deficient Mice

scholarly journals Regulatory T cell-mediated resolution of lung injury: identification of potential target genes via expression profiling

2010 ◽  
Vol 41 (2) ◽  
pp. 109-119 ◽  
Author(s):  
Neil R. Aggarwal ◽  
Franco R. D'Alessio ◽  
Kenji Tsushima ◽  
Venkataramana K. Sidhaye ◽  
Christopher Cheadle ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lung Injury ◽  
Acute Phase ◽  
Adoptive Transfer ◽  
Target Genes ◽  
Expression Studies ◽  
Rag 1 ◽  
Gene Expression Studies ◽  
Gene Ontologies ◽  
Deficient Mice

In animal models of acute lung injury (ALI), gene expression studies have focused on the acute phase of illness, with little emphasis on resolution. In this study, the acute phase of intratracheal lipopolysaccharide (IT LPS)-induced lung injury was similar in wild-type (WT) and recombinase-activating gene-1-deficient (Rag-1−/−) lymphocyte-deficient mice, but resolution was impaired and resolution-phase lung gene expression remained different from baseline only in Rag-1−/− mice. By focusing on groups of genes involved in similar biological processes (gene ontologies) pertinent to inflammation and the immune response, we identified 102 genes at days 4 and 10 after IT LPS with significantly different expression between WT and Rag-1−/− mice. After adoptive transfer of isolated CD4+CD25+Foxp3+ regulatory T cells (Tregs) to Rag-1−/− mice at the time of IT LPS, resolution was similar to that in WT mice. Of the 102 genes distinctly changed in either WT or Rag-1−/− mice from our 7 gene ontologies, 19 genes reverted from the Rag-1−/− to the WT pattern of expression after adoptive transfer of Tregs, implicating those 19 genes in Treg-mediated resolution of ALI.

scholarly journals NOX2 protects against progressive lung injury and multiple organ dysfunction syndrome

2014 ◽  
Vol 307 (1) ◽  
pp. L71-L82 ◽  
Author(s):  
Laura C. Whitmore ◽  
Kelli L. Goss ◽  
Elizabeth A. Newell ◽  
Brieanna M. Hilkin ◽  
Jessica S. Hook ◽  
...  
Keyword(s):  
Lung Injury ◽  
Organ Dysfunction ◽  
Systemic Inflammation ◽  
Multiple Organ Dysfunction Syndrome ◽  
Murine Model ◽  
Oxidant Stress ◽  
Multiple Organ ◽  
Multiple Organ Dysfunction ◽  
Cellular Analysis ◽  
Deficient Mice

Systemic inflammatory response syndrome (SIRS) is a common clinical condition in patients in intensive care units that can lead to complications, including multiple organ dysfunction syndrome (MODS). MODS carries a high mortality rate, and it is unclear why some patients resolve SIRS, whereas others develop MODS. Although oxidant stress has been implicated in the development of MODS, several recent studies have demonstrated a requirement for NADPH oxidase 2 (NOX2)-derived oxidants in limiting inflammation. We recently demonstrated that NOX2 protects against lung injury and mortality in a murine model of SIRS. In the present study, we investigated the role of NOX2-derived oxidants in the progression from SIRS to MODS. Using a murine model of sterile systemic inflammation, we observed significantly greater illness and subacute mortality in gp91phox−/y(NOX2-deficient) mice compared with wild-type mice. Cellular analysis revealed continued neutrophil recruitment to the peritoneum and lungs of the NOX2-deficient mice and altered activation states of both neutrophils and macrophages. Histological examination showed multiple organ pathology indicative of MODS in the NOX2-deficient mice, and several inflammatory cytokines were elevated in lungs of the NOX2-deficient mice. Overall, these data suggest that NOX2 function protects against the development of MODS and is required for normal resolution of systemic inflammation.

Alveolar macrophage apoptosis and TNF-α, but not p53, expression correlate with murine response to bleomycin

1998 ◽  
Vol 275 (6) ◽  
pp. L1208-L1218 ◽  
Author(s):  
Luis A. Ortiz ◽  
Kryztof Moroz ◽  
Jing-Yao Liu ◽  
Gary W. Hoyle ◽  
Timothy Hammond ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Lung Injury ◽  
Alveolar Macrophage ◽  
Tumor Necrosis ◽  
Annexin V ◽  
P53 Expression ◽  
Tnf Α ◽  
Induction Of Apoptosis ◽  
Deficient Mice ◽  
Necrosis Factor

Apoptosis is considered to be a protective mechanism that limits lung injury. However, apoptosis might contribute to the inflammatory burden present in the injured lung. The exposure of mice to bleomycin (BLM) is a well-established model for the study of lung injury. BLM exposure induces DNA damage and enhances tumor necrosis factor (TNF)-α expression in the lung. To evaluate the importance of alveolar macrophage (AM) apoptosis in the pathogenesis of lung injury, we exposed BLM-sensitive (C57BL/6) and BLM-resistant (BALB/c) mice to BLM (120 mg/kg) and studied the induction of apoptosis [by light-microscopy changes (2, 8, 12, 24, 48, and 72 h) and annexin V uptake by flow cytometry (24 h)], the secretion of TNF-α (measured by ELISA), and the expression of p53 (by immunoblotting) in AM retrieved from these mice. BLM, but not vehicle, induced apoptosis in AM from both murine strains. The numbers of apoptotic AM were significantly greater ( P < 0.001) in C57BL/6 mice (52.9%) compared with BALB/c mice (40.8%) as demonstrated by annexin V uptake. BLM induction of apoptosis in AM was preceded by an increased secretion of TNF-α in C57BL/6 but not in BALB/c mice. Furthermore, double TNF-α receptor-deficient mice, developed on a C57BL/6 background, demonstrated significantly ( P < 0.001) lower numbers of apoptotic AM compared with C57BL/6 and BALB/c mice. BLM also enhanced p53 expression in AM from both murine strains. However, p53-deficient mice developed BLM-induced lung injury, exhibited similar lung cell proliferation (measured as proliferating cell nuclear antigen immunostaining), and accumulated similar amounts of lung hydroxyproline (65 ± 6.9 μg/lung) as did C57BL/6 (62 ± 6.5 μg/lung) mice. Therefore, AM apoptosis is occurring during BLM-induced lung injury in a manner that correlates with murine strain sensitivity to BLM. Furthermore, TNF-α secretion rather than p53 expression contributes to the difference in murine strain response to BLM. tumor necrosis factor; strain susceptibility

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