Abstract:
BACKGROUND:ExoU, a Pseudomonas aeruginosa cytotoxin with phospholipase A2 activity, was shown to induce vascular hyperpermeability and thrombus formation in a murine model of pneumosepsis. In this study, we investigated the toxin ability to induce alterations in pulmonary fibrinolysis and the contribution of the platelet activating factor (PAF) in the ExoU-induced overexpression of plasminogen activator inhibitor-1 (PAI-1). METHODS:Mice were intratracheally instilled with the ExoU producing PA103 P. aeruginosa or its mutant with deletion of the exoU gene. After 24 h, animal bronchoalveolar lavage fluids (BALF) were analyzed and lung sections were submitted to fibrin and PAI-1 immunohistochemical localization. Supernatants from A549 airway epithelial cells and THP-1 macrophage cultures infected with both bacterial strains were also analyzed at 24 h post-infection. RESULTS:In PA103-infected mice, but not in control animals or in mice infected with the bacterial mutant, extensive fibrin deposition was detected in lung parenchyma and microvasculature whereas mice BALF exhibited elevated tissue factor-dependent procoagulant activity and PAI-1 concentration. ExoU-triggered PAI-1 overexpression was confirmed by immunohistochemistry. In in vitro assays, PA103-infected A549 cells exhibited overexpression of PAI-1 mRNA. Increased concentration of PAI-1 protein was detected in both A549 and THP-1 culture supernatants. Mice treatment with a PAF antagonist prior to PA103 infection reduced significantly PAI-1 concentrations in mice BALF. Similarly, A549 cell treatment with an antibody against PAF receptor significantly reduced PAI-1 mRNA expression and PAI-1 concentrations in cell supernatants, respectively. CONCLUSION:ExoU was shown to induce disturbed fibrin turnover, secondary to enhanced procoagulant and antifibrinolytic activity during P. aeruginosa pneumosepsis, by a PAF-dependent mechanism. Besides its possible pathophysiological relevance, in vitro detection of exoU gene in bacterial clinical isolates warrants investigation as a predictor of outcome of patients with P. aeruginosa pneumonia/sepsis and as a marker to guide treatment strategies.
journal_name
Respir Resjournal_title
Respiratory researchauthors
Machado GB,de Oliveira AV,Saliba AM,de Lima CD,Suassuna JH,Plotkowski MCdoi
10.1186/1465-9921-12-104subject
Has Abstractpub_date
2011-08-05 00:00:00pages
104eissn
1465-9921issn
1465-993Xpii
1465-9921-12-104journal_volume
12pub_type
杂志文章abstract::The aim was to compare the diagnosis of COPD among smokers according to different international guidelines and to compare the outcome when using slow (SVC) and forced vital capacity (FVC). In order to find current smokers a questionnaire was sent to persons who had been on sick leave for more than two weeks. Those who...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-8-89
更新日期:2007-12-04 00:00:00
abstract:BACKGROUND:The discrepancy between functional and inflammatory airway response to ozone has been reported in normal subjects, but few data are available for stable asthmatics regularly treated with inhaled corticosteroids. METHODS:Twenty-three well controlled, regularly treated, mild-to-moderate asthmatic patients und...
journal_title:Respiratory research
pub_type: 杂志文章,随机对照试验
doi:10.1186/1465-9921-11-5
更新日期:2010-01-19 00:00:00
abstract::There is an increasing interest in the potential of exhaled biomarkers, such as volatile organic compounds (VOCs), to improve accurate diagnoses and management decisions in pulmonary diseases. The objective of this manuscript is to systematically review the current knowledge on exhaled VOCs with respect to their poten...
journal_title:Respiratory research
pub_type: 杂志文章,meta分析,评审
doi:10.1186/1465-9921-13-117
更新日期:2012-12-21 00:00:00
abstract:BACKGROUND:Several studies have investigated the prevalence and risk factors of insomnia in subjects with obstructive sleep apnea syndrome. However, few studies have investigated the prevalence and risk factors for obstructive sleep apnea syndrome in insomnia sufferers. Thus, the aim of this study was to examine the pr...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-017-0616-8
更新日期:2017-07-06 00:00:00
abstract:BACKGROUND:Mutations in the eukaryotic translation initiation factor 2α kinase 4 (EIF2AK4) gene have recently been identified in recessively inherited veno-occlusive disease. In this study we assessed if EIF2AK4 mutations occur also in a family with autosomal dominantly inherited pulmonary arterial hypertension (HPAH) ...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-016-0457-x
更新日期:2016-11-04 00:00:00
abstract:BACKGROUND:During 2007-2010, the National Health and Nutrition Examination Survey (NHANES) conducted a spirometry component which obtained pre-bronchodilator pulmonary lung function data on a nationally representative sample of US adults aged 6-79 years and post-bronchodilator pulmonary lung function data for the subse...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-14-103
更新日期:2013-10-09 00:00:00
abstract:BACKGROUND:Possible variation in bronchodilator response (BDR) according to age at the diagnosis of adult-onset asthma is unknown. Our aim was to assess if BDR in FEV1 is related to age at diagnosis of adult-onset asthma and how many subjects fulfill the 400 mL criterion of BDR, the suggested cut-off for asthma-like re...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-020-01441-w
更新日期:2020-07-13 00:00:00
abstract:BACKGROUND:Retinoid X receptors (RXRs) are members of the nuclear receptor (NR) superfamily that mediate signalling by 9-cis retinoic acid, a vitamin A derivative. RXRs play key roles not only as homodimers but also as heterodimeric partners, e.g., for retinoic acid receptors, vitamin D receptors, and peroxisome prolif...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-018-0963-0
更新日期:2019-01-03 00:00:00
abstract:BACKGROUND:Recent consensus statements demonstrate the breadth of the chronic rhinosinusitis (CRS) differential diagnosis. However, the classification and mechanisms of different CRS phenotypes remains problematic. METHOD:Statistical patterns of subjective and objective findings were assessed by retrospective chart re...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-6-149
更新日期:2005-12-19 00:00:00
abstract:BACKGROUND:Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive fibrotic lung disease for which there is no cure. Current therapeutics are only able to slow disease progression, therefore there is a need to explore alternative, novel treatment options. There is increasing evidence that the 3', 5' cyclic ade...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-018-0759-2
更新日期:2018-04-07 00:00:00
abstract:BACKGROUND:25-hydroxycholesterol (25-HC) is one of the oxysterols, which are oxidized derivatives of cholesterol, and has been reported to be involved in the pathogenesis of atherosclerosis and Alzheimer's disease. In lung, the possible involvement of 25-HC in airway diseases has been revealed. In the present study, we...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-13-63
更新日期:2012-07-31 00:00:00
abstract:BACKGROUND:The relationship between the Epworth sleepiness scale (ESS) and the apnea-hypopnea index (AHI) is uncertain and even poor. The major problem associated with the ESS might be a lack of consideration of weight in prediction in clinical practice. Would awarding different item-scores to the four scales of ESS it...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-020-01417-w
更新日期:2020-06-12 00:00:00
abstract:BACKGROUND:Myofibroblasts, proposed as being derived from circulating fibrocytes, are considered to be important cells in thickening of the basement membrane in patients with asthma. We have studied the correlation of tissue fibrocyte levels to basement membrane thickness and the presence of fibrocytes in bronchoalveol...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-7-50
更新日期:2006-03-29 00:00:00
abstract:BACKGROUND:Exposure to cigarette smoke is considered a major risk factor for the development of lung diseases, since its causative role has been assessed in the induction and maintenance of an inflamed state in the airways. Lung fibroblasts can contribute to these processes, due to their ability to produce proinflammat...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-8-23
更新日期:2007-03-12 00:00:00
abstract:BACKGROUND:ABCA3 transporter (ATP-binding cassette transporter of the A subfamily) is localized to the limiting membrane of lamellar bodies, organelles for assembly and storage of pulmonary surfactant in alveolar epithelial type II cells (AECII). It transports surfactant phospholipids into lamellar bodies and absence o...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-12-4
更新日期:2011-01-07 00:00:00
abstract:BACKGROUND:The coexistence of COPD and asthma is widely recognized but has not been well described. This study characterizes clinical features, spirometry, and chest CT scans of smoking subjects with both COPD and asthma. METHODS:We performed a cross-sectional study comparing subjects with COPD and asthma to subjects ...
journal_title:Respiratory research
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1186/1465-9921-12-127
更新日期:2011-09-27 00:00:00
abstract:BACKGROUND:There are limited series concerning Dieulafoy disease of the bronchus. We describe the clinical presentation of a series of 7 patients diagnosed with Dieulafoy disease of the bronchus and provide information about the pathological diagnosis approach. PATIENTS AND METHODS:A retrospective review of patients w...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-9-58
更新日期:2008-08-05 00:00:00
abstract:BACKGROUND:Exposure to ozone activates innate immune function and causes neutrophilic (PMN) airway inflammation that in some individuals is robustly elevated. The interplay between immuno-inflammatory function and genomic signaling in those with heightened inflammatory responsiveness to ozone is not well understood. O...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-13-89
更新日期:2012-10-03 00:00:00
abstract:BACKGROUND:Steroid resistant (SR) asthma is characterized by persistent airway inflammation that fails to resolve despite treatment with high doses of corticosteroids. Furthermore, SR patient airways show increased numbers neutrophils, which are less responsive to glucocorticoid. The present study seeks to determine wh...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-016-0462-0
更新日期:2016-11-16 00:00:00
abstract:BACKGROUND:Apoptosis has recently been proposed to contribute to the pathogenesis of emphysema. METHODS:In order to establish if cell fate plays a role even in end-stage disease we studied 16 lungs (9 smoking-associated and 7 alpha1antitrypsin (AAT)-deficiency emphysema) from patients who had undergone lung transplant...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-6-14
更新日期:2005-02-10 00:00:00
abstract:BACKGROUND:Early life impairments leading to lower lung function by adulthood are considered as risk factors for chronic obstructive pulmonary disease (COPD). Recently, we compared the lung transcriptomic profile between two mouse strains with extreme total lung capacities to identify plausible pulmonary function deter...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-018-0795-y
更新日期:2018-06-06 00:00:00
abstract:BACKGROUND:Little is known about the association between cigarette smoking and asthma severity. We assessed smoking as a determinant of disease severity and control in a cohort of clinic-referred allergic subjects who developed new onset asthma. METHODS:Allergic rhinitis subjects with no asthma (n = 371) were followed...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-12-16
更新日期:2011-01-24 00:00:00
abstract::The transcription factors nuclear factor interleukin-6 (NF-IL6), early growth response-1 (EGR-1) and hypoxia-inducible factor-1 (HIF-1) have important roles in the molecular pathophysiology of hypoxia-associated pulmonary disease. NF-IL6 controls the production of interleukin (IL)-6 in vascular endothelial cells, whic...
journal_title:Respiratory research
pub_type: 杂志文章,评审
doi:10.1186/rr27
更新日期:2000-01-01 00:00:00
abstract::Mitogen-activated protein kinase (MAPK) phosphatase 1 (MKP-1) is a protein with anti-inflammatory properties and the archetypal member of the dual-specificity phosphatases (DUSPs) family that have emerged over the past decade as playing an instrumental role in the regulation of airway inflammation. Not only does MKP-1...
journal_title:Respiratory research
pub_type: 杂志文章,评审
doi:10.1186/s12931-017-0637-3
更新日期:2017-08-10 00:00:00
abstract:BACKGROUND:Numerous studies have demonstrated associations between genetic markers and COPD, but results have been inconsistent. One reason may be heterogeneity in disease definition. Unsupervised learning approaches may assist in understanding disease heterogeneity. METHODS:We selected 31 phenotypic variables and 12 ...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-11-30
更新日期:2010-03-16 00:00:00
abstract:BACKGROUND:Various signals are known to participate in the pathogenesis of lung fibrosis. Our aim was to determine which signal is predominantly mobilized in the early inflammatory phase and thereafter modulates the development of lung fibrosis. METHODS:Mice received a single dose of 3 mg/kg body weight of bleomycin (...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-015-0261-z
更新日期:2015-08-20 00:00:00
abstract:BACKGROUND:We have recently reported that protein phosphate 2A (PP2A) inactivation resulted in increased phosphorylation of the mitogen-activated protein kinase (MAPK) c-Jun N-terminal kinase 1 (JNK1) and glucocorticoid receptors (GR) at Ser(226), thereby reducing GR nuclear translocation and causing corticosteroid ins...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-016-0349-0
更新日期:2016-03-24 00:00:00
abstract:BACKGROUND:Inhaled furosemide offers a potentially novel treatment for dyspnoea, which may reflect modulation of pulmonary stretch receptor feedback to the brain. Specificity of relief is unclear because different neural pathways may account for different components of clinical dyspnoea. Our objective was to evaluate i...
journal_title:Respiratory research
pub_type: 杂志文章,随机对照试验
doi:10.1186/s12931-018-0886-9
更新日期:2018-09-20 00:00:00
abstract:OBJECTIVE:We aimed to identify the prevalence and distribution patterns of allergens among Chinese children with asthma/asthma-like symptoms (ALS). METHODS:A total of 3479 children with asthma/ALS were enrolled. Skin prick test (SPT) was used to test the allergen-specific IgE. We analysed allergens prevalence and dist...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-020-1318-1
更新日期:2020-02-18 00:00:00
abstract:BACKGROUND:Pulmonary inflammation, oxidants-antioxidants imbalance, as well as innate and adaptive immunity have been proposed as playing a key role in the development of COPD. The role of vitamins, as assessed either by food frequency questionnaires or measured in serum levels, have been reported to improve pulmonary ...
journal_title:Respiratory research
pub_type: 杂志文章,meta分析,评审
doi:10.1186/1465-9921-11-171
更新日期:2010-12-06 00:00:00