Abstract:
RATIONALE:The generation of protective secretory IgA relies on the epithelial polymeric immunoglobulin receptor (pIgR). pIgR expression is reduced in chronic obstructive pulmonary disease (COPD), but correlation to disease severity and underlying mechanisms remains unknown. OBJECTIVES:To address the hypothesis that pIgR down-regulation in COPD concerns severe disease in relation to aberrant programming of the bronchial epithelium. METHODS:Surgical lung tissue and primary bronchial epithelium (cultured in air-liquid interface, ALI) obtained from a large series of patients (n = 116) were studied for pIgR expression and regulation. MEASUREMENTS AND MAIN RESULTS:pIgR immunostaining in the bronchial epithelium is decreased in severe COPD. In contrast, pIgR transcription was up-regulated in smokers with or without COPD. In ALI (vs. submerged) cultures, pIgR expression was strongly induced, whereas pIgR expression and IgA-transcytosis capacity were decreased in cultures from subjects with severe COPD as compared with control subjects. In addition, COPD cultures released more transforming growth factor-β1 (TGF-β1), reflecting increased epithelial TGF-β1 immunostaining in COPD lung tissue. Finally, besides inducing epithelial dedifferentiation, exogenous TGF-β1 dose-dependently inhibited pIgR production, whereas pIgR increased on blockade of TGF-β1 activity during ALI differentiation. CONCLUSIONS:pIgR down-regulation in COPD correlates with disease severity, and the bronchial epithelium reconstituted in vitro from these patients retains its aberrant imprinting for pIgR expression. This study also links pIgR down-regulation to TGF-β-driven reprogramming of the bronchial epithelium, which results in impaired lung IgA immunity in patients with COPD.
journal_name
Am J Respir Crit Care Medauthors
Gohy ST,Detry BR,Lecocq M,Bouzin C,Weynand BA,Amatngalim GD,Sibille YM,Pilette Cdoi
10.1164/rccm.201311-1971OCsubject
Has Abstractpub_date
2014-09-01 00:00:00pages
509-21issue
5eissn
1073-449Xissn
1535-4970journal_volume
190pub_type
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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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abstract::Alkaline phosphatase (ALP) in lung lavage fluids is a marker of tissue damage and type II cell proliferation. Type II pneumocytes are extensively involved in fibrosis. The aim of our study was to verify whether local ALP activity can be held as a marker of fibrosis in chronic interstitial lung disorders. ALP was deter...
journal_title:American journal of respiratory and critical care medicine
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pub_type: 临床试验,杂志文章
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journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.153.4.8616570
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abstract::To investigate the utility of testing all tuberculosis patients for HIV infection in Los Angeles, we prospectively evaluated 183 hospitalized patients with acid-fast smear-positive tuberculosis who gave no history of HIV infection. HIV serologic testing was performed, and the presence of risk factors for HIV infection...
journal_title:American journal of respiratory and critical care medicine
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journal_title:American journal of respiratory and critical care medicine
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journal_title:American journal of respiratory and critical care medicine
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abstract::Sarcoidosis is a systemic, granulomatous disorder with a high rate of spontaneous remission indicating the presence of antiinflammatory mechanisms. Antiinflammatory mediators such as interleukin-10 (IL-10) and transforming growth factor-beta (TGF-beta) should be able to induce spontaneous remission of sarcoidosis. By ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章
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更新日期:1996-09-01 00:00:00
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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
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更新日期:2001-06-01 00:00:00
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abstract::The predisposing factors and complications of unplanned extubation (UEX) in mechanically ventilated adult patients are not well recognized. We designed a prospective multicenter observational study to identify risk factors and describe the complications of UEX. We followed 426 ventilated patients over a 2-mo period. C...
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:1998-04-01 00:00:00
abstract::The role of nutritional status in the prognosis of subjects with severe chronic obstructive pulmonary disease was studied in a cohort of Canadian men and women followed for 3 to 5 yr. A total of 348 subjects who were recruited for a study of negative pressure ventilation were evaluated for lung function and body weigh...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.153.3.8630580
更新日期:1996-03-01 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
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更新日期:2018-07-15 00:00:00