Abstract:
RATIONALE:The mechanisms by which oxidants are sensed by cells and cause inflammation are not well understood. OBJECTIVES:This study aimed to determine how cells "sense" soluble oxidants and how this is translated into an inflammatory reaction. METHODS:Monocytes, macrophages, or HEK293 cells (stably transfected with human Toll-like receptor [TLR]2, TLR2/1, TLR2/6, or TLR4/MD2-CD14) were used. CXC ligand-8 (CXCL8) levels were measured using ELISA. Phosphorylated IL-1 receptor-associated kinase 1 levels were measured using Western blot. TLR2(-/-) and TLR4(-/-) mice were challenged with oxidants, and inflammation was measured by monitoring cell infiltration and KC levels. MEASUREMENTS AND MAIN RESULTS:Oxidants evoked the release of CXCL8 from monocytes/macrophages; this was abrogated by pretreatment with N-acetylcysteine or binding antibodies to TLR2 and was associated with the rapid phosphorylation of IL-1 receptor-associated kinase 1. Oxidants added to HEK293 cells transfected with TLR2, TLR1/2, or TLR2/6 but not TLR4/MD2-CD14 or control HEK nulls resulted in the release of CXCL8. Oxidant challenge delivered intraperitoneally (2-24 hours) or by inhalation to the lungs (3 days) resulted in a robust inflammation in wild-type mice. TLR2(-/-) mice did not respond to oxidant challenge in either model. TLR4(-/-) mice responded as wild-type mice to oxidants at 2 hours but as TLR2(-/-) mice at later time points. CONCLUSIONS:Oxidant-TLR2 interactions provide a signal that initiates the inflammatory response.
journal_name
Am J Respir Crit Care Medauthors
Paul-Clark MJ,McMaster SK,Sorrentino R,Sriskandan S,Bailey LK,Moreno L,Ryffel B,Quesniaux VF,Mitchell JAdoi
10.1164/rccm.200707-1019OCsubject
Has Abstractpub_date
2009-02-15 00:00:00pages
299-306issue
4eissn
1073-449Xissn
1535-4970pii
200707-1019OCjournal_volume
179pub_type
杂志文章abstract:RATIONALE:Congenital central hypoventilation syndrome (CCHS) is a genetic disorder mainly characterized by failure of automatic control of breathing, causing alveolar hypoventilation. Little is known regarding cough in CCHS. Parental reports indicate that patients cough normally during airway infections; however, previ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200612-1870OC
更新日期:2007-10-15 00:00:00
abstract:RATIONALE:IL-4 and IL-13 share many biological functions important in the development of allergic airway inflammation and are implicated in the pathogenesis of asthma. AMG 317 is a fully human monoclonal antibody to IL-4Ralpha that blocks both IL-4 and IL-13 pathways. OBJECTIVES:To evaluate efficacy and safety of AMG ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,随机对照试验
doi:10.1164/rccm.200909-1448OC
更新日期:2010-04-15 00:00:00
abstract:RATIONALE:Patients with obstructive sleep apnea (OSA) adapt to the anatomical vulnerability of their upper airway by generating increased activity in upper airway-dilating muscles during wakefulness. Norepinephrine (NE) and serotonin (5-HT) mediate, through α₁-adrenergic and 5-HT₂A receptors, a wake-related excitatory ...
journal_title:American journal of respiratory and critical care medicine
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doi:10.1164/rccm.200912-1884OC
更新日期:2010-11-15 00:00:00
abstract::Many patients who develop incapacitating illness have not expressed clear treatment preferences. Therefore, surrogate decision makers are asked to make judgments about what treatment pathway is most consistent with the patient's values. Surrogates often struggle with such decisions. The difficulty arises because answe...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,评审
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abstract::Cryptogenic fibrosing alveolitis has been reported to be associated with an increased risk of lung cancer. However, it has recently become apparent that cigarette smoking may be a risk factor for cryptogenic fibrosing alveolitis as well as for lung cancer, and so may confound the association between these conditions. ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.161.1.9906062
更新日期:2000-01-01 00:00:00
abstract::Disordered breathing during sleep is associated with acute, unfavorable effects on cardiovascular physiology, but few studies have examined its postulated association with cardiovascular disease (CVD). We examined the cross-sectional association between sleep- disordered breathing and self-reported CVD in 6,424 free-l...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,多中心研究
doi:10.1164/ajrccm.163.1.2001008
更新日期:2001-01-01 00:00:00
abstract::The present study was undertaken to determine if a synthetic peptide, KLLLLKLLLLKLLLLKLLLLK (KL4), in which K = lysine and L = leucine, in an aqueous dispersion of phospholipids (DPPC and POPG), would expand pulmonary alveoli and improve gas exchange in premature human infants with respiratory distress syndrome (RDS)....
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.153.1.8542150
更新日期:1996-01-01 00:00:00
abstract:RATIONALE:Few studies have examined associations between exposure to air pollution and childhood lung function after implementation of strict air quality regulations in the 1990s. OBJECTIVES:To assess traffic-related pollution exposure and childhood lung function. METHODS:We geocoded addresses for 614 mother-child pa...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201506-1058OC
更新日期:2016-04-15 00:00:00
abstract::Rationale: Guidelines for vasopressor titration suggest a universal target-mean arterial pressure (MAP) >65 mm Hg. The implications for patients with premorbid low/high blood pressure are unknown.Objectives: To investigate the relationship between premorbid blood pressure and vasopressor duration for patients with sho...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201908-1681OC
更新日期:2020-07-01 00:00:00
abstract:RATIONALE:chronic obstructive pulmonary disease (COPD), characterized by airflow limitation, is a disorder with high phenotypic and genetic heterogeneity. Pulmonary emphysema is a major but variable component of COPD; familial data suggest that different components of COPD, such as emphysema, may be influenced by speci...
journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章
doi:10.1164/rccm.201004-0541OC
更新日期:2011-01-01 00:00:00
abstract::Based on serial lung function measurements performed in 142 children (68 males; 74 females) with cystic fibrosis (CF), prospectively evaluated over an age range of 6 to 20 years, we attempted to determine whether the lung clearance index (LCI) as a measure of ventilation inhomogeneities could be a discriminating facto...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200407-948OC
更新日期:2005-02-15 00:00:00
abstract::Elevated levels of ambient particulate matter (PM(10)) have been associated with increased cardiopulmonary morbidity and mortality. We previously showed that the deposition of particles in the lung induces a systemic inflammatory response that includes stimulation of the bone marrow. This marrow response is related to...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.164.5.2010160
更新日期:2001-09-01 00:00:00
abstract::Tracheal and lung parenchymal SP-LI (substance P-like immunoreactivity) and VIP-LI (vasoactive intestinal peptide-like immunoreactivity) content was measured in HPLC-purified tissue extracts from patients with and without asthma. We detected significantly less SP-LI in tracheal tissue from asthmatic than from nonasthm...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.151.2.7531100
更新日期:1995-02-01 00:00:00
abstract:RATIONALE:The airway surface liquid, the thin layer of liquid covering the airways, is essential for mucociliary clearance and as a barrier against microbial and other noxious agents. Proteins secreted into the airway surface liquid by epithelial and nonepithelial cells may be important in innate immunity and to improv...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200409-1185OC
更新日期:2005-11-01 00:00:00
abstract::We examined the influence of gender on the polysomnographic features of obstructive sleep apnea (OSA) in a retrospective study of 830 patients with OSA diagnosed by overnight polysomnography (PSG). The severity of OSA was determined from the apnea- hypopnea index (AHI) for total sleep time (AHI(TST)), and was classifi...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.161.5.9904121
更新日期:2000-05-01 00:00:00
abstract::It is generally accepted that tuberculosis results from a single infection with a single Mycobacterium tuberculosis strain. Such infections are thought to confer protective immunity against exogenous reinfection. In this study, a novel polymerase chain reaction method was developed to specifically identify M. tubercul...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200305-714OC
更新日期:2004-03-01 00:00:00
abstract:RATIONALE:An objective and simple prognostic model for patients with pulmonary embolism could be helpful in guiding initial intensity of treatment. OBJECTIVES:To develop a clinical prediction rule that accurately classifies patients with pulmonary embolism into categories of increasing risk of mortality and other adve...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200506-862OC
更新日期:2005-10-15 00:00:00
abstract::The present prospective study was designed to determine the prevalence of pleural effusion at approximately 28 days after cardiac surgery and their subsequent course. This consecutive case study included 389 patients; 312 had only coronary artery bypass graft surgery (CABG) surgery, 37 had both valve and CABG surgery,...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200203-184OC
更新日期:2002-12-15 00:00:00
abstract:RATIONALE:Spirometric detection of airway obstruction in adults requires separate predictive formulae for each ethnicity and sex for percentage of FEV(1)/FVC (%FEV(1)/FVC) and percentage of FEV(3)/FVC (%FEV(3)/FVC), the major measurements for defining airway obstruction. OBJECTIVES:To eliminate the need for multiple f...
journal_title:American journal of respiratory and critical care medicine
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doi:10.1164/rccm.200604-517OC
更新日期:2006-09-01 00:00:00
abstract::We have tested two surfactant preparations with the same phospholipid (PL) composition, containing recombinant surfactant protein-C (rSP-C surfactant) and without SP-C (plain PL surfactant). The effects of rSP-C surfactant were compared with the bovine-derived surfactant preparations Alveofact, bLES, and Infasurf in a...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.158.1.9712061
更新日期:1998-07-01 00:00:00
abstract::Many patients with acute asthma do not respond adequately to currently accepted therapy, including oxygen, beta-agonists, and corticosteroids. Leukotriene receptor antagonists such as montelukast have demonstrated efficacy in chronic asthma, but their efficacy in acute asthma is unknown. In this randomized, double-bli...
journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1164/rccm.200208-802OC
更新日期:2003-02-15 00:00:00
abstract::To investigate interactions between the endothelium and leukocytes in patients with sepsis, we measured soluble adhesion molecules (sE-selectin and sICAM-1), von Willebrand factor antigen (vWf:Ag), myeloperoxidase (MPO), and lactoferrin (Lacto-f) as plasma markers of endothelial and neutrophil activation. We tested wh...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.157.3.9705034
更新日期:1998-03-01 00:00:00
abstract::Small airway disease is thought to contribute significantly to functional impairment caused by asthma. Functional evidence of airway-parenchyma uncoupling in asthma, such as loss of deep breath bronchodilator effect in bronchoconstrictive episodes and enhanced airway closure, has been previously demonstrated. Elastic ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200403-305OC
更新日期:2004-10-15 00:00:00
abstract::It has been nearly a century since the first suggestion that a soluble factor in plasma or serum might be responsible for the symptoms of allergic disease and asthma, and more than 30 yr since immunoglobulin E (IgE) was identified as the key molecule in mediating what are now described as type 1 hypersensitivity react...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,评审
doi:10.1164/ajrccm.164.supplement_1.2103024
更新日期:2001-10-15 00:00:00
abstract::Exogenous surfactant therapy is not standard in the acute respiratory distress syndrome (ARDS) because of a lack of proven benefit. Nonuniform surfactant distribution after either bolus or aerosol administration may be an important factor limiting response. In a previous study of acute lung injury, we demonstrated tha...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.158.1.9704119
更新日期:1998-07-01 00:00:00
abstract::The interleukin-1 cluster on human chromosome 2q12-2q14 harbors various promising candidate genes for asthma and other inflammatory diseases. We conducted a systematic association study with single-nucleotide polymorphisms (SNPs) located in candidate genes situated in this cluster. Single-marker, two-locus and three-l...
journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1164/rccm.200302-281OC
更新日期:2004-06-01 00:00:00
abstract::We have studied intrasubject variability with respect to counts of immunostained inflammatory cells in snap frozen endobronchial biopsies from a group of patients with clinically mild to moderate stable asthma. Fiberoptic bronchoscopy was used to obtain endobronchial biopsies from the upper and lower lobes in 12 volun...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.153.3.8630570
更新日期:1996-03-01 00:00:00
abstract:RATIONALE:Chronic lung diseases are associated with cardiovascular disease. How these associations evolve from young adulthood forward is unknown. Understanding the preclinical history of these associations could inform prevention strategies for common heart-lung conditions. OBJECTIVES:To use the Coronary Artery Risk ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201501-0116OC
更新日期:2015-07-01 00:00:00
abstract::Colony-forming units of Mycobacterium tuberculosis in sputum were counted at 2-day intervals in 100 patients treated with 22 regimens of isoniazid, rifampin, pyrazinamide, ethambutol, or streptomycin, given alone or in combinations. The exponential fall in colony-forming units was measured by linear regression coeffic...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200210-1125OC
更新日期:2003-05-15 00:00:00
abstract::Cigarette smoking causes the development of chronic bronchitis and chronic obstructive pulmonary disease. We hypothesized that exposure to cigarette smoke might initiate release of inflammatory mediators by bronchial epithelial cells. To evaluate this, the effect of cigarette smoke extract (CSE) on IL-8 release from c...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.155.5.9154890
更新日期:1997-05-01 00:00:00