Abstract:
RATIONALE:Platelets may interact with the immune system in tuberculosis (TB) to regulate human inflammatory responses that lead to morbidity and spread of infection. OBJECTIVES:To identify a functional role of platelets in the innate inflammatory and matrix-degrading response in TB. METHODS:Markers of platelet activation were examined in plasma from 50 patients with TB before treatment and 50 control subjects. Twenty-five patients were followed longitudinally. Platelet-monocyte interactions were studied in a coculture model infected with live, virulent Mycobacterium tuberculosis (M.tb) and dissected using qRT-PCR, Luminex multiplex arrays, matrix degradation assays, and colony counts. Immunohistochemistry detected CD41 (cluster of differentiation 41) expression in a pulmonary TB murine model, and secreted platelet factors were measured in BAL fluid from 15 patients with TB and matched control subjects. MEASUREMENTS AND MAIN RESULTS:Five of six platelet-associated mediators were upregulated in plasma of patients with TB compared with control subjects, with concentrations returning to baseline by Day 60 of treatment. Gene expression of the monocyte collagenase MMP-1 (matrix metalloproteinase-1) was upregulated by platelets in M.tb infection. Platelets also enhanced M.tb-induced MMP-1 and -10 secretion, which drove type I collagen degradation. Platelets increased monocyte IL-1 and IL-10 and decreased IL-12 and MDC (monocyte-derived chemokine; also known as CCL-22) secretion, as consistent with an M2 monocyte phenotype. Monocyte killing of intracellular M.tb was decreased. In the lung, platelets were detected in a TB mouse model, and secreted platelet mediators were upregulated in human BAL fluid and correlated with MMP and IL-1β concentrations. CONCLUSIONS:Platelets drive a proinflammatory, tissue-degrading phenotype in TB.
journal_name
Am J Respir Crit Care Medauthors
Fox KA,Kirwan DE,Whittington AM,Krishnan N,Robertson BD,Gilman RH,López JW,Singh S,Porter JC,Friedland JSdoi
10.1164/rccm.201710-2102OCsubject
Has Abstractpub_date
2018-07-15 00:00:00pages
245-255issue
2eissn
1073-449Xissn
1535-4970journal_volume
198pub_type
杂志文章abstract::Normoxic lung ischemia/reperfusion (I/R) leads to oxidative injury of the pulmonary tissue. We analyzed angiotensin-converting enzyme (ACE) in perfused rat lungs upon I/R in order to assess the endothelial injury produced. I/R led to a time-dependent increase in ACE activity in the perfusate, from 145+/-14 mU to 252+/...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.156.4.96-12116
更新日期:1997-10-01 00:00:00
abstract:RATIONALE:Dyspnea is the impairing cardinal symptom of asthma but its accurate perception is also crucial for timely initiation of treatment. However, the underlying brain mechanisms of perceived dyspnea in patients with asthma are unknown. OBJECTIVES:To study brain mechanisms of dyspnea in asthma. METHODS:By using f...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200902-0300OC
更新日期:2009-08-01 00:00:00
abstract:RATIONALE:Studies in humans and rodents have indicated a causative role for CD8(+) T cells in IgE-mediated allergic inflammation, but their function is still controversial. OBJECTIVES:To analyze the role of allergen-specific CD8(+) T cells during the development of allergic airway inflammation in two parallel but dive...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200902-0190OC
更新日期:2010-01-01 00:00:00
abstract:RATIONALE:No methodical assessment of the lung, cardiac, and sleep function of patients surviving an acute hypercapnic respiratory failure episode requiring admission to the intensive care unit (ICU) has been reported in the literature. OBJECTIVES:To prospectively investigate the prevalence and impact of comorbidities...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201608-1666OC
更新日期:2017-07-15 00:00:00
abstract::Collections of sputum from 105 patients with newly diagnosed pulmonary tuberculosis were made before and at 1 and 2 d after the start of chemotherapy with isoniazid (INH) alone given to groups of patients in doses of 600 mg, 300 mg, 150 mg, 75 mg, 37.5 mg, 18.75 mg, and 9 mg daily, as well as from an untreated group. ...
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.156.3.9609132
更新日期:1997-09-01 00:00:00
abstract::The aim of this study was to assess positive end-expiratory pressure (PEEP)-induced lung overdistension and alveolar recruitment in six patients with acute lung injury (ALI) using a computed tomographic (CT) scan method. Lung overdistension was first determined in six healthy volunteers in whom CT sections were obtain...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.158.5.9802101
更新日期:1998-11-01 00:00:00
abstract:RATIONALE:Lung allografts are prone to reperfusion injury and acute rejection, which, in addition to infiltrating lymphocytes, are accompanied by neutrophil infiltration and neutrophil-associated oxidative stress. Indoleamine 2,3-dioxygenase (IDO) is a unique cytosolic enzyme that possesses T-cell-suppressive and antio...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200509-1413OC
更新日期:2006-03-01 00:00:00
abstract::The distribution of ventilation-perfusion (VA/Q) ratios during bronchoconstriction measured with the multiple inert gases elimination technique is frequently bimodal. However, the topographic basis and the cause of that bimodality remain unknown. In this article, regional VA/Q is quantified by three-dimensional positr...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200409-1296OC
更新日期:2005-04-01 00:00:00
abstract:RATIONALE:Pulmonary hypertension (PH) is a life-threatening disease, characterized by vascular remodeling and vasoconstriction. Evidence suggests that oxidative stress may contribute to the pathogenesis and/or development of PH. OBJECTIVES:In the present study, we examined whether intratracheal gene transfer of human ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200702-264OC
更新日期:2008-01-15 00:00:00
abstract::Previous studies reported linkage between maternally inherited atopy and the beta subunit of the high affinity IgE receptor (Fc epsilon RI-beta) located on chromosome 11q13. We have investigated 45 Italian families with atopic asthmatic children, for a total of 213 subjects, including 148 patients. Genotyping was carr...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.153.5.8630620
更新日期:1996-05-01 00:00:00
abstract:RATIONALE:Pulmonary complications (PCs) cause significant morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HCT). Shifts in gut microbiota have been linked to HCT outcomes; however, their effect on PCs is unknown. OBJECTIVES:To investigate whether changes in gut microbiota are associate...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201507-1491OC
更新日期:2016-08-15 00:00:00
abstract::The aim of this study was to compare the effects of salmeterol and beclomethasone on lung function and symptoms in children with mild to moderate asthma. Sixty-seven children not treated with inhaled corticosteroids were randomized in a double-blind parallel study either to salmeterol 50 micrograms b.i.d. or beclometh...
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.156.3.9611067
更新日期:1997-09-01 00:00:00
abstract::The frequency and determinants of exogenous reinfection and of endogenous reactivation of tuberculosis in patients previously treated are poorly understood. In Gran Canaria Island, Spain, between 1991 and 1996, 962 tuberculosis cases were confirmed by culture. Drug susceptibility testing was performed on available bac...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.163.3.2003070
更新日期:2001-03-01 00:00:00
abstract::The cost effectiveness of asthma care is the first topic of the National Asthma Education and Prevention Program Task Force Report on the Cost Effectiveness, Quality of Care, and Financing of Asthma Care. This working group characterized the role of health economics in understanding optimal asthma management strategie...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm/154.3_Pt_2.S84
更新日期:1996-09-01 00:00:00
abstract::Bronchopulmonary dysplasia (BPD) is a chronic lung disease of very low birth weight infants, associated with oxygen therapy, barotrauma, and/or infections. Improved medical care has led to a paradoxically increased incidence of BPD due to greater infant survival. Early prediction of BPD has proven challenging. Increas...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.165.8.2108044
更新日期:2002-04-15 00:00:00
abstract::Exhaled nitric oxide (NO) remains a promising noninvasive index for monitoring inflammatory lung diseases; however, the plateau concentration (C(NO,plat)) is nonspecific and requires a constant exhalation flow rate. We utilized a new technique that employs a variable flow rate to estimate key flow-independent paramete...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.165.3.2105098
更新日期:2002-02-01 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::This study describes the natural history of atopic and wheezy disorders from birth to adult life in a cohort at risk of atopy. One hundred subjects born in Poole, England, were selected at birth in 1976 on the basis that at least one parent was atopic. Subjects were examined annually in the preschool years, and at the...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.165.2.2104032
更新日期:2002-01-15 00:00:00
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journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.159.6.9807060
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abstract::The expression of renin-angiotensin system components and the elevation of angiotensin-converting enzyme (ACE) in a number of fibrotic lung diseases suggests angiotensin II (AII) could play a role in the pathogenesis of pulmonary fibrosis. However, the effect of AII on lung fibroblasts has not previously been assessed...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.161.6.9907004
更新日期:2000-06-01 00:00:00
abstract::Partial liquid ventilation (PLV) has been shown to be an effective means of improving oxygenation in the injured lung. However, little is known about how approach to ventilation during PLV affects gas exchange and pulmonary mechanics. We hypothesized that gas exchange and pulmonary mechanics would be best with positiv...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.159.4.9711021
更新日期:1999-04-01 00:00:00
abstract::Pulmonary emphysema and periodontal disease are each characterized by the uncontrolled proteolysis of connective tissue proteins by proteinases derived from human neutrophils. Although these diseases would not appear to be related in terms of the initial insult to individual tissues, the ultimate result in each diseas...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,评审
doi:10.1164/ajrccm/150.6_Pt_2.S143
更新日期:1994-12-01 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::Respiratory system compliance (Crs) in infants with cystic fibrosis (CF) has been reported as decreased or not different compared with healthy control subjects; however, the reported measurements of Crs were "quasi-static" or by the single-breath occlusion technique, with all measurements limited to tidal lung volume,...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200401-132OC
更新日期:2004-09-01 00:00:00
abstract::Current evidence suggests that patients with obstructive sleep apnea (OSA) may have augmented pharyngeal dilator muscle activity during wakefulness, to compensate for deficient anatomy. However, the isolated effect of sleep on the activity of these muscles (comparing OSA patients with controls) has not been studied. W...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.153.6.8665050
更新日期:1996-06-01 00:00:00
abstract:RATIONALE:In San Francisco, 70% of the tuberculosis cases occur among foreign-born persons, mainly from China, the Philippines, and Mexico. We postulate that there are differences in the characteristics and risk factors for tuberculosis among these populations. OBJECTIVES:To determine the clinical, epidemiological and...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201212-2239OC
更新日期:2013-05-01 00:00:00
abstract:RATIONALE:The role of computed tomography (CT) screening for lung cancer is controversial, currently under study, and not yet fully elucidated. OBJECTIVES:To report findings from initial and 1-year repeat screening low-radiation-dose CT of the chest and 3-year outcomes for 50- to 79-year-old current and ex-smokers in ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200802-336OC
更新日期:2008-11-01 00:00:00
abstract::Although considerable evidence indicates a role for CD4(+) T lymphocytes (T cells) in airway inflammation, little data exist regarding the mechanisms underlying the induction and regulation of CD4(+) T cell reactivity to lung-specific antigens. To dissect the immunologic and molecular mechanisms of CD4(+) T cell dysre...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200404-464OC
更新日期:2004-12-01 00:00:00
abstract:RATIONALE:E-cigarettes vaporize propylene glycol/vegetable glycerin (PG/VG), nicotine, and flavorings. However, the long-term health effects of exposing lungs to vaped e-liquids are unknown. OBJECTIVES:To determine the effects of chronic vaping on pulmonary epithelia. METHODS:We performed research bronchoscopies on h...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201710-2033OC
更新日期:2018-07-01 00:00:00
abstract:RATIONALE:Constitutive activation of the epidermal growth factor receptor (EGFR) is prevalent in epithelial cancers, particularly in non-small cell lung carcinoma (NSCLC). Mutations identified in EGFR predict the sensitivity to EGFR-targeted therapy. Detection of these mutations is mainly based on tissue biopsy, which ...
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.201406-1003OC
更新日期:2014-11-15 00:00:00