Responses of the Lung to Toxic Injury

Witschi, Hanspeter

doi:10.2307/3430660

Cited by 43 publications

(11 citation statements)

References 44 publications

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“…These results were confirmed the following year by KUWANO et al [25] through a similar study of bleomycininduced lung fibrosis in mice, in which the caspase inhibitor was administered by aerosol. Regardless of the route of drug delivery, the blockade of collagen deposition in vivo by a specific inhibitor of apoptosis suggests that the fibrotic response is secondary to the apoptotic death of certain lung cell types, and is consistent with the theories put forth by WITSCHI [23] and ADAMSON et al [24].…”

Section: Apoptosis In Lung Fibrosissupporting

confidence: 85%

“…The same research group showed that the induction of lung fibrosis by intratracheal instillation of bleomycin is associated with upregulation of Fas on the epithelium and concomitant induction of epithelial apoptosis as a prelude to fibrogenesis [10]. These results support the hypothesis proposed years earlier by WITSCHI [23] and ADAMSON et al [24], which suggests that the destruction of the healthy alveolar epithelium, in itself, creates a profibrotic microenvironment that initiates a nascent fibrotic focus. Consistent with that interpretation, the author9s study of lung biopsies from patients with IPF has shown that nascent fibrotic foci colocalise with apoptotic or absent alveolar epithelium [7].…”

Section: Apoptosis In Lung Fibrosissupporting

confidence: 72%

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Epithelial apoptosis in the initiation of lung fibrosis

Uhal

2003

European Respiratory Journal

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Section: Apoptosis In Lung Fibrosissupporting

confidence: 85%

Section: Apoptosis In Lung Fibrosissupporting

confidence: 72%

Epithelial apoptosis in the initiation of lung fibrosis

Uhal

2003

European Respiratory Journal

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“…Following injury, the alveolar epithelium needs to be rapidly and properly repaired. Any delay in the re-epithelialization process may impair the healing response by allowing proliferation of fibroblasts in the interstitium and consequently the excessive accumulation of fibrotic tissue in the air spaces [128]. At the present time, little is known on the factors involved in the repair of the alveolar structure in patients with lung diseases [129].…”

Section: Management Of Lung Diseases In Childrenmentioning

confidence: 99%

Bronchoalveolar lavage in children

Blic¹,

Midulla²,

Barbato³

et al. 2000

eur respir j

350

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Bronchoalveolar lavage (BAL) is routinely performed in adults for sampling cellular and biochemical components. Many studies have been performed that have enabled the proposal of recommendations for BAL, methodology and processing, as well as reference values in different clinical settings. In contrast, despite a world-wide increase in the use of BAL in children, including neonates, there are, at the present time, no clear recommendations on the methodology, the clinical applications and the research areas for BAL. A Task Force on BAL in children has been approved by the European Respiratory Society (ERS) Task Force committee 1996. The objectives of this task force were: 1) to provide recommendations and guidelines on how to perform BAL and how to process the return fluid in children; 2) to collect and discuss available reference values; 3) to list indications and results in both immunocompetent and immunocompromised children; 4) to define areas for future research.This task force included paediatric respiratory physicians involved in bronchoscopy and BAL and was run as a collaboration between the Paediatric Bronchology Group and the BAL scientific group of the ERS.

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“…For many years the alveolar epithelium of the fibrotic human lung has been described as the ''hyperplastic'' or ''cuboidal'' epithelium, based on the observation of predominantly type II pneumocytes that are proliferating in response to ongoing epithelial injury [17,18]. In contrast, the alveolar epithelium of normal lung is essentially quiescent, with few or no proliferating cells and numerous type I cells, the terminally differentiated progeny of type II cells [19].…”

Section: Introductionmentioning

confidence: 99%

Cell cycle dependence of ACE-2 explains downregulation in idiopathic pulmonary fibrosis

Uhal

Dang

et al. 2012

Eur Respir J

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Alveolar epithelial type II cells, a major source of angiotensin-converting enzyme (ACE)-2 in the adult lung, are normally quiescent but actively proliferate in lung fibrosis and downregulate this protective enzyme. It was, therefore, hypothesised that ACE-2 expression might be related to cell cycle progression.To test this hypothesis, ACE-2 mRNA levels, protein levels and enzymatic activity were examined in fibrotic human lungs and in the alveolar epithelial cell lines A549 and MLE-12 studied at postconfluent (quiescent) versus subconfluent (proliferating) densities.ACE-2 mRNA, immunoreactive protein and enzymatic activity were all high in quiescent cells, but were severely downregulated or absent in actively proliferating cells. Upregulation of the enzyme in cells that were progressing to quiescence was completely inhibited by the transcription blocker actinomycin D or by SP600125, an inhibitor of c-Jun N-terminal kinase (JNK). In lung biopsy specimens obtained from patients with idiopathic pulmonary fibrosis, immunoreactive enzyme was absent in alveolar epithelia that were positive for proliferation markers, but was robustly expressed in alveolar epithelia devoid of proliferation markers.These data explain the loss of ACE-2 in lung fibrosis and demonstrate cell cycle-dependent regulation of this protective enzyme by a JNK-mediated transcriptional mechanism. @ERSpublications Cell cycle-dependent regulation of ACE-2 by a JNK-mediated transcriptional mechanism explains ACE-2 downregulation in IPF

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Responses of the Lung to Toxic Injury

Cited by 43 publications

References 44 publications

Epithelial apoptosis in the initiation of lung fibrosis

Epithelial apoptosis in the initiation of lung fibrosis

Bronchoalveolar lavage in children

Cell cycle dependence of ACE-2 explains downregulation in idiopathic pulmonary fibrosis

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