Abstract:
RATIONALE:Studies in patients and experimental animals provide compelling evidence of the involvement of the major thrombin receptor, proteinase-activated receptor-1 (PAR(1)), and the potent chemokine, chemokine (CC motif) ligand-2 (CCL2)/monocyte chemotactic protein-1, in the pathogenesis of idiopathic pulmonary fibrosis (IPF). PAR(1) knockout mice are protected from bleomycin-induced lung inflammation and fibrosis and this protection is associated with marked attenuation in CCL2 induction. OBJECTIVES:The aim of this study was to determine which cell types represent the major source of PAR(1)-inducible CCL2 in the fibrotic lung. METHODS:Using immunohistochemistry and dual immunofluorescence, we examined PAR(1) and CCL2 expression in the bleomycin model and human IPF lung. PAR(1) and CCL2 gene expression was also assessed in laser-captured alveolar septae from patients with IPF. The ability of PAR(1) to induce CCL2 production by lung epithelial cells was also examined in vitro. MEASUREMENTS AND MAIN RESULTS:We report for the first time that PAR(1) and CCL2 are coexpressed and co-up-regulated on the activated epithelium in fibrotic areas in IPF. Similar observations were found in bleomycin-induced lung injury. Furthermore, we show that thrombin is a potent inducer of CCL2 gene expression and protein release by cultured lung epithelial cells via a PAR(1)-dependent mechanism. CONCLUSIONS:These data support the notion that PAR(1) activation on lung epithelial cells may represent an important mechanism leading to increased local CCL2 release in pulmonary fibrosis. Targeting PAR(1) on the pulmonary epithelium may offer a unique opportunity for therapeutic intervention in pulmonary fibrosis and other inflammatory and fibroproliferative conditions associated with excessive local generation of thrombin and CCL2 release.
journal_name
Am J Respir Crit Care Medauthors
Mercer PF,Johns RH,Scotton CJ,Krupiczojc MA,Königshoff M,Howell DC,McAnulty RJ,Das A,Thorley AJ,Tetley TD,Eickelberg O,Chambers RCdoi
10.1164/rccm.200712-1827OCsubject
Has Abstractpub_date
2009-03-01 00:00:00pages
414-25issue
5eissn
1073-449Xissn
1535-4970pii
200712-1827OCjournal_volume
179pub_type
杂志文章abstract::The aim of this study was to clarify the influence of gastroesophageal reflux (GER) on cough threshold in patients with digestive symptoms but free from respiratory involvement. Of 57 consecutive subjects referred for 24-h esophageal pH monitoring because of digestive reflux symptoms, 29 patients free from respiratory...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.151.2.7842220
更新日期:1995-02-01 00:00:00
abstract::Luteolin is a flavonoid that has been shown to reduce proinflammatory molecule expression in vitro. In the present study, we have tested the ability of luteolin to inhibit lipopolysaccharide (LPS)- induced lethal toxicity and proinflammatory molecule expression in vivo. Mice receiving LPS (Salmonella enteriditis LPS, ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.165.6.2101049
更新日期:2002-03-15 00:00:00
abstract:RATIONALE:T-bet (TBX21 or T-box 21) is a critical regulator of T-helper 1 lineage commitment and IFN-gamma production. Knockout mice lacking T-bet develop airway hyperresponsiveness (AHR) to methacholine, peribronchial eosinophilic and lymphocytic inflammation, and increased type III collagen deposition below the bronc...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200503-505OC
更新日期:2006-01-01 00:00:00
abstract::There is a subgroup of cigarette smokers who are more susceptible than others to the deleterious effects of cigarette smoke and to chronic airflow obstruction. The study of histopathologic and physiologic differences between these "susceptible" smokers and "resistant" smokers, who do not develop clinically significant...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,评审
doi:10.1164/ajrccm.149.6.7911710
更新日期:1994-06-01 00:00:00
abstract::The clinical significance of minimal acute rejection (grade A1) in lung transplant recipients is unknown. We prospectively analyzed 1,159 transbronchial lung biopsies in 184 patients. Two hundred seventy-nine biopsies in 128 participants confirmed A1 histology at a mean postoperative day of 229 +/- 340. Sixty four of ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200302-165OC
更新日期:2004-11-01 00:00:00
abstract::The relationship of sleep-disordered breathing (SOB) to neuropsychological deficits was investigated with cross-sectional data from the Wisconsin Sleep Cohort Study, a population-based study of the natural history of SDB. A sample of 841 employed men and women ages 30 to 60 yr was studied by overnight polysomnography ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.156.6.9610026
更新日期:1997-12-01 00:00:00
abstract::The timing and magnitude of airway narrowing in central apneas is unknown. We have developed a method of apnea classification that relies on the transmission of cardiac airflow oscillation to indicate airway patency. Using a theoretical model, we showed that the amplitude of the cardiac airflow oscillation is proporti...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.157.2.9612125
更新日期:1998-02-01 00:00:00
abstract::Dobutamine has been proposed as a means of disclosing a pathologic oxygen supply (DO2) dependency in critically ill patients. Like other catecholamines, however, dobutamine might increase cellular metabolism, so that oxygen consumption (VO2) would increase regardless of the presence or absence of a supply dependency. ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.150.1.8025780
更新日期:1994-07-01 00:00:00
abstract::In mechanically ventilated neonates, the instrumental dead space is a major determinant of total minute ventilation. By flushing this dead space, continuous tracheal gas insufflation (CTGI) may allow reduction of the risk of overinflation. We conducted a randomized trial to evaluate the efficacy of CTGI in reducing ai...
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
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更新日期:2000-09-01 00:00:00
abstract::Rationale: Recent studies have demonstrated that extracellular vesicles (EVs) released during acute lung injury (ALI) were inflammatory.Objectives: The current study was undertaken to test the role of EVs induced and released from severe Escherichia coli pneumonia (E. coli EVs) in the pathogenesis of ALI and to determ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201812-2296OC
更新日期:2019-11-15 00:00:00
abstract::We used three-dimensional reconstructions obtained with spiral computed tomography to measure total diaphragm surface area (Adi), and the surface area of the dome (Ado) and of the zone of apposition (Aap) of the diaphragm in nine patients with single-lung transplantation (SLT) for emphysema and nine normal subjects ma...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.159.6.9812052
更新日期:1999-06-01 00:00:00
abstract::Levels of oleic acid (OA) are elevated in plasma and bronchoalveolar lavage fluids of patients with acute respiratory distress syndrome (ARDS). OA is also widely used to provoke edema, by unknown mechanisms, in experimental models of ARDS. We investigated the impact of intravascularly applied OA on epithelial lining f...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200407-954OC
更新日期:2005-03-01 00:00:00
abstract::The inflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha) and interleukin-1-beta (IL-1 beta), have been associated with accelerated metabolism and protein turnover following exogenous administration in normal humans. We hypothesized that these inflammatory cytokines might contribute to the weight-losing proc...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.153.2.8564110
更新日期:1996-02-01 00:00:00
abstract:BACKGROUND:The clinical utility of bronchoalveolar lavage fluid (BAL) cell analysis for the diagnosis and management of patients with interstitial lung disease (ILD) has been a subject of debate and controversy. The American Thoracic Society (ATS) sponsored a committee of international experts to examine all relevant l...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,实务指引
doi:10.1164/rccm.201202-0320ST
更新日期:2012-05-01 00:00:00
abstract::To determine the incidence and 90-d mortality of acute respiratory failure (ARF), acute lung injury (ALI), and the acute respiratory distress syndrome (ARDS), we carried out an 8-wk prospective cohort study in Sweden, Denmark, and Iceland. All intensive care unit (ICU) admissions (n = 13,346) >/= 15 yr of age were ass...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.159.6.9808136
更新日期:1999-06-01 00:00:00
abstract::Previous study of adrenergic control of the tracheal vasculature in rats (1) demonstrated that beta-adrenergic blockade heightened arteriolar and large venular contractile responses to norepinephrine, a nonselective alpha-adrenergic agonist. The present study was undertaken to confirm the presence of functional beta-a...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.153.3.8630550
更新日期:1996-03-01 00:00:00
abstract:RATIONALE:Little is known about human club cells, dome-shaped cells with dense cytoplasmic granules and microvilli that represent the major secretory cells of the human small airways (at least sixth-generation bronchi). OBJECTIVES:To define the ontogeny and biology of the human small airway epithelium club cell. METH...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201710-2107OC
更新日期:2018-12-01 00:00:00
abstract::To attain a better understanding of antibiotic cycling and its effects on the epidemiology of antibiotic resistance in gram-negative microorganisms, two different antibiotic classes (quinolone and beta-lactam) were cycled during four 4-month periods in a surgical intensive care unit. Respiratory aspirates and rectal s...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200401-070OC
更新日期:2005-03-01 00:00:00
abstract::Although impairment of gas exchange caused by ventilation-perfusion (VA/Q) mismatch has been extensively analyzed, there have been no systematic studies focused on determining the distributions of diffusion properties in dose connection with those of VA/Q. We attempted to clarify the simultaneous distributions of VA/Q...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.156.1.9607090
更新日期:1997-07-01 00:00:00
abstract:RATIONALE:Ipsilateral recurrence rates of spontaneous pneumothorax after video-assisted thoracoscopic surgery are higher than rates after open thoracotomy. OBJECTIVES:This study was conducted to determine whether additional minocycline pleurodesis would be effective in diminishing recurrence after video-assisted thora...
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.200509-1414OC
更新日期:2006-03-01 00:00:00
abstract::Female Fisher 344 rats (n = 25) were inoculated intrapleurally with a single 20-mg dose of (JM-100) fibrous glass. The mean length (2.2 microns) and width (0.15 microns) of the fibrous glass particles was within respirable range. Following inoculation, the rats were killed at timed intervals ranging from 2 to 430 d fr...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.150.2.8049840
更新日期:1994-08-01 00:00:00
abstract::The aim of this study was to assess the influence of preservation solution type and extra- or intracellular composition on the occurrence of early graft dysfunction after clinical lung transplantation. For 170 patients who underwent a single (n = 124) or bilateral (n = 46) lung transplantation in two centers in Paris ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.164.7.2012135
更新日期:2001-10-01 00:00:00
abstract::Epidemiological data indicate that living or working in a moldy building is associated with increased risk of respiratory symptoms and disease related to inflammatory reactions, but biochemical evidence linking cause and effect is still scarce. The staff working in a mold-contaminated school, and a reference group wit...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.160.6.9903023
更新日期:1999-12-01 00:00:00
abstract::We used various ovalbumin sensitization and challenge protocols to determine the importance of the route of allergen administration and the genetic background in modulating the physiologic, inflammatory, and immunologic features characteristic of allergen-induced asthma. In BALB/c mice, induction of maximal airway hyp...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.155.2.9032210
更新日期:1997-02-01 00:00:00
abstract:RATIONALE:Neutrophils are key players in chronic obstructive pulmonary disease (COPD), and increased numbers of neutrophils are present in sputum and lung tissue of patients with COPD. Interestingly, immunoglobulin free light chains (IgLC) are able to prolong the life of neutrophils; therefore, IgLC may contribute to t...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201104-0761OC
更新日期:2012-04-15 00:00:00
abstract:RATIONALE:Obstructive sleep apnea (OSA) is associated with impaired renal function, but uncertainty exists over whether OSA treatment can influence renal outcomes. OBJECTIVES:To determine the effects of continuous positive airway pressure (CPAP) on renal function in subjects with coexisting OSA and cardiovascular dise...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,多中心研究
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更新日期:2017-12-01 00:00:00
abstract::Noninvasive and invasive diagnostic techniques have been shown to achieve comparable performances in the evaluation of suspected ventilator-associated pneumonia (VAP). We studied the impact of both approaches on outcome in a prospective, open, and randomized study in three intensive care units (ICUs) of a 1,000-bed te...
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/ajrccm.162.1.9907090
更新日期:2000-07-01 00:00:00
abstract:RATIONALE:In cigarette smoking-induced chronic obstructive pulmonary disease, structural and functional derangements are characterized by parenchymal destruction and pulmonary hypertension. Statins are 3-hydroxy-3-methyl-glutaryl-coenzyme-A reductase inhibitors that have been used as lipid-lowering agents. These drugs ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200501-041OC
更新日期:2005-10-15 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
pub_type: 杂志文章
doi:10.1164/rccm.200912-1884OC
更新日期:2010-11-15 00:00:00
abstract:RATIONALE:Drug-resistant tuberculosis transmission in hospitals threatens staff and patient health. Surgical face masks used by patients with tuberculosis (TB) are believed to reduce transmission but have not been rigorously tested. OBJECTIVES:We sought to quantify the efficacy of surgical face masks when worn by pati...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201107-1190OC
更新日期:2012-05-15 00:00:00