Abstract:
RATIONALE:5-Hydroxytryptamine (5-HT) is involved in the pathogenesis of allergic airway inflammation (AAI). It is unclear, however, how 5-HT contributes to AAI and whether this depends on tryptophan hydroxylase (TPH) 1, the critical enzyme for peripheral 5-HT synthesis. OBJECTIVES:To elucidate the role of TPH1 and the peripheral source of 5-HT in asthma pathogenesis. METHODS:TPH1-deficient and TPH1-inhibitor-treated animals were challenged in ovalbumin and house dust mite models of AAI. Experiments with bone marrow chimera, mast cell-deficient animals, platelets transfusion, and bone marrow dendritic cells (BMDC) driven model of AAI were performed. 5-HT levels were measured in bronchoalveolar lavage fluid or serum of animals with AAI and in human asthma. MEASUREMENTS AND MAIN RESULTS:5-HT levels are increased in bronchoalveolar lavage fluid of mice and people with asthma after allergen provocation. TPH1 deficiency and TPH1 inhibition reduced all cardinal features of AAI. Administration of exogenous 5-HT restored AAI in TPH1-deficient mice. The pivotal role of 5-HT production by structural cells was corroborated by bone marrow chimera experiments. Experiments in mast cell-deficient mice revealed that mast cells are not a source of 5-HT, whereas transfusion of platelets from wild-type and TPH1-deficient mice revealed that only platelets containing 5-HT enhanced AAI. Lack of endogenous 5-HT in vitro and in vivo was associated with an impaired Th2-priming capacity of BMDC. CONCLUSIONS:In summary, TPH1 deficiency or inhibition reduces AAI. Platelet- and not mast cell-derived 5-HT is pivotal in AAI, and lack of 5-HT leads to an impaired Th2-priming capacity of BMDC. Thus, targeting TPH1 could offer novel therapeutic options for asthma.
journal_name
Am J Respir Crit Care Medauthors
Dürk T,Duerschmied D,Müller T,Grimm M,Reuter S,Vieira RP,Ayata K,Cicko S,Sorichter S,Walther DJ,Virchow JC,Taube C,Idzko Mdoi
10.1164/rccm.201208-1440OCsubject
Has Abstractpub_date
2013-03-01 00:00:00pages
476-85issue
5eissn
1073-449Xissn
1535-4970pii
rccm.201208-1440OCjournal_volume
187pub_type
杂志文章abstract::Inhaled nitric oxide (NO) improves systemic oxygenation (PaO2/FIO2) in adult patients with acute respiratory distress syndrome (ARDS). However, individual response varies, and previous trials demonstrated no outcome benefit. This prospective, randomized study in 40 ARDS patients analyzed dose-response (DR) characteris...
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.2108121
更新日期:2003-04-01 00:00:00
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::Surfactant protein B (SP-B) is one of the essential constituents of the alveolar surfactant system, presenting mainly in the form of SP-B dimer. The measurement of this molecule in biologic samples has been hampered by its extreme hydrophobicity and intimate association with surfactant lipids. We developed a solid-pha...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.152.5.7582290
更新日期:1995-11-01 00:00:00
abstract::Nitric oxide (NO) produced in the airways can be either detrimental or protective to the host. To investigate the role of NO in the pathogenesis of exercise-induced bronchoconstriction (EIB), we measured exhaled NO (ENO) after exercise challenge in 39 asthmatic and six normal children. FEV(1) and ENO were measured bef...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.164.10.2009105
更新日期:2001-11-15 00:00:00
abstract::To determine if gastric intramucosal pH changes during weaning from mechanical ventilation are related to gastric mucosal blood flow modifications, we studied 16 ventilator-supported patients with chronic obstructive pulmonary disease (COPD) who tolerated a 2-h trial of spontaneous breathing with pressure support vent...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.160.5.9901018
更新日期:1999-11-01 00:00:00
abstract::We investigated the relation between IgE reactive with histamine-releasing factor (HRF) and clinical status in patients with asthma or rhinitis. Sera were used to passively sensitize purified, lactic-acid treated basophils. IgE-independent HRF due to chemokines was removed from mononuclear cell supernatants with hepar...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.154.2.8756800
更新日期:1996-08-01 00:00:00
abstract::Recently described surgical approaches to the treatment of emphysema, including buttressed stapled volume reduction and laser coagulation, are associated with variable clinical outcomes. We examined objective preoperative factors as predictors of response to treatment in patients enrolled in a randomized trial of stap...
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.155.4.9105070
更新日期:1997-04-01 00:00:00
abstract::Theophylline is well-established in the management of asthma, and there is some evidence of an antiinflammatory effect in asthma. It is not known whether theophylline affects inflammatory markers such as sputum eosinophils and exhaled nitric oxide (NO) in patients with mild asthma not receiving inhaled steroid therapy...
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.164.2.2006043
更新日期:2001-07-15 00:00:00
abstract::Airway remodeling may lead to irreversible loss of lung function in asthma. The impact of childhood asthma, airway responsiveness, atopy, and smoking on airway remodeling was investigated in a birth cohort studied longitudinally to age 26. A low postbronchodilator ratio of forced exhaled volume in 1 second (FEV1) to v...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.2108009
更新日期:2002-06-01 00:00:00
abstract::We developed clonal cell lines of human bronchial smooth muscle origin by retroviral transduction of temperature-sensitive simian virus 40 large tumor (T) antigen. These cells show increased growth potential at 33 degrees C, but on shift to the nonpermissive temperature (39 degrees C), they show diminished or arrested...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200307-964OC
更新日期:2004-03-15 00:00:00
abstract::Respiratory syncytial virus (RSV) is the major pathogen responsible for acute bronchiolitis in infancy. However, evaluation of the relative importance of rhinovirus or multiple viral infections has been hampered by the lack of sensitive diagnostic methodologies. Therefore, in this study we used the reverse transcripti...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200112-118BC
更新日期:2002-05-01 00:00:00
abstract::This study examines hemodialysis clearances of isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), and ethambutol (EMB). Seven chronic hemodialysis patients were studied. Six were given single oral doses (INH 300 mg, RIF 600 mg, PZA 1000 mg, and EMB 25 mg/kg) 2 h before hemodialysis (Cobe Centrysystem 3 hemodialysis ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.159.5.9810034
更新日期:1999-05-01 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::The gender-and race-specific effects of asthma/wheeze on pulmonary function level and annual growth velocity were studied in a cohort of 10,792 white and 944 black children 6 to 18 yr of age, examined annually between 1974 and 1989 in six U.S. cities. In comparison with white boys who never reported asthma or wheeze, ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.149.5.8173760
更新日期:1994-05-01 00:00:00
abstract::The role of lipoxygenase metabolites in the pathogenesis of endotoxin (LPS)-induced lung injury remains to be clarified. We investigated the contribution of peptide leukotrienes to LPS-induced acute lung injury using a potent antagonist, ONO-1078 (ONO). Experimental groups consisted of a saline group (n = 10), an LPS ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.150.5.7952560
更新日期:1994-11-01 00:00:00
abstract::Rationale: Decisions in medicine are made on the basis of knowledge and reasoning, often in shared conversations with patients and families in consideration of clinical practice guideline recommendations, individual preferences, and individual goals. Observational studies can provide valuable knowledge to inform guide...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.202010-3943ST
更新日期:2021-01-01 00:00:00
abstract::Noninflammatory structural alterations, variously referred to as airway remodeling, are well documented in the asthmatic airway. However, the pathogenesis of these alterations, the importance of airway remodeling in generating the asthma phenotype, and the natural history of airway remodeling responses have not been a...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.164.supplement_2.2106070
更新日期:2001-11-15 00:00:00
abstract:RATIONALE:Reactivation tuberculosis (TB) occurs as a result of reactivation of latent TB infection (LTBI), and was reported to occur in the United States at a rate of 0.10 to 0.16 cases per 100 person-years in the 1950s; it has not been measured since. OBJECTIVES:To calculate the rate of reactivation TB in a U.S. comm...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200909-1355OC
更新日期:2010-08-01 00:00:00
abstract:RATIONALE:Nitric oxide (NO), synthesized by NOSs (NO synthases), plays a role in the development of pulmonary hypertension (PH). However, the role of NO/NOSs in bone marrow (BM) cells in PH remains elusive. OBJECTIVES:To determine the role of NOSs in BM cells in PH. METHODS:Experiments were performed on 36 patients w...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201709-1783OC
更新日期:2018-07-15 00:00:00
abstract::We have previously reported differential impairment of pulmonary and systemic vascular contractility in hyperdynamic sepsis. The objectives of this study were (1) to determine whether the magnitude of this phenomenon depends on the control group chosen for comparison, and (2) to examine the role of nitric oxide (NO) i...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm/151.3_Pt_1.706
更新日期:1995-03-01 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:RATIONALE:Tezacaftor (formerly VX-661) is an investigational small molecule that improves processing and trafficking of the cystic fibrosis transmembrane conductance regulator (CFTR) in vitro, and improves CFTR function alone and in combination with ivacaftor. OBJECTIVES:To evaluate the safety and efficacy of tezacaft...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1164/rccm.201704-0717OC
更新日期:2018-01-15 00:00:00
abstract::The effects of glutathione-S-transferase (GST) M1, GSTT1, and GSTP1 genotypes on lung function growth were investigated in 1,940 children enrolled in the Children's Health Study as fourth graders (aged 8-11 years) in two cohorts during 1993 and 1996 and were followed annually over a 4-year period. Genotypes for GSTM1 ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.2112065
更新日期:2002-09-01 00:00:00
abstract:RATIONALE:Exhaled carbon monoxide (CO) and arterial blood carboxyhemoglobin concentrations (Hb-CO) increase in inflammatory pulmonary diseases. OBJECTIVES:To study whether arterial Hb-CO is useful to monitor disease activity in patients with chronic obstructive pulmonary disease (COPD) who had stopped smoking. METHOD...
journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章
doi:10.1164/rccm.200407-914OC
更新日期:2005-06-01 00:00:00
abstract::To elucidate which cells are synthesizing tenascin in usual interstitial pneumonia (UIP) we have analyzed thoracoscopic or open lung biopsies from 30 patients with UIP by mRNA in situ hybridization, using (35)S-labeled tenascin RNA probes. The phenotype of the cells expressing tenascin mRNA was confirmed by immunohist...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.161.3.9809115
更新日期:2000-03-01 00:00:00
abstract::Asthma is a chronic inflammatory disease that persists even during adequate therapy and asymptomatic episodes. We questioned whether "silent" chronic allergen exposure can induce and maintain airway inflammation and whether this still occurs during regular treatment with inhaled steroids. Twenty-six patients with hous...
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.2112097
更新日期:2002-08-01 00:00:00
abstract:RATIONALE:The contribution of interferon-gamma release assays (IGRAs) to appropriate risk stratification of active tuberculosis suspects has not been studied. OBJECTIVES:To determine whether the addition of quantitative IGRA results to a prediction model incorporating clinical criteria improves risk stratification of ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200906-0981OC
更新日期:2010-01-01 00:00:00
abstract:RATIONALE:Obstructive sleep apnea (OSA) is associated with several pathophysiological deficits found in diabetic retinopathy (DR). Hence, it's plausible that OSA could play a role in the pathogenesis of sight-threatening DR (STDR). OBJECTIVES:To assess the relationship between OSA and DR in patients with type 2 diabet...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201701-0175OC
更新日期:2017-10-01 00:00:00
abstract::Lymphangioleiomyomatosis (LAM), a disease that occurs primarily in women, is characterized by cystic lung lesions causing respiratory failure, which may require lung transplantation. Lung diffusion (DLCO) and/or FEV1 are decreased, but frequently not in parallel with each other. Because cardiopulmonary exercise testin...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200206-593OC
更新日期:2003-12-15 00:00:00
abstract::The nasal antiinflammatory effects produced by maintenance treatment with topical steroids include reduced production of cytokines. The present study explored nasal mucosal effects induced during the first 9 h after a single dose of topical budesonide. Nine subjects with allergic rhinitis due to birch or timothy polle...
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.162.5.9910094
更新日期:2000-11-01 00:00:00