Abstract:
:Mechanical ventilation with high tidal volumes has been associated with pulmonary alveolar flooding. Understanding the mechanisms underlying cyclic stretch-induced increases in alveolar epithelial permeability may be important in designing preventive measures for acute lung injury. In this work, we assessed whether cyclic stretch leads to the generation of reactive oxygen species in type I-like alveolar epithelial cells, which increase monolayer permeability via activation of NF-κB and extracellular signal-regulated kinase (ERK). We cyclically stretched type I-like rat primary alveolar epithelial cells at magnitudes of 12, 25, and 37% change in surface area (ΔSA) for 10 to 120 minutes. High levels of reactive oxygen species and of superoxide and NO specifically were detected in cells stretched at 37% ΔSA for 10 to 120 minutes. Exogenous superoxide and NO stimulation increased epithelial permeability in unstretched cells, which was preventable by the NF-κB inhibitor MG132. The cyclic stretch-induced increase in permeability was decreased by the superoxide scavenger tiron and by MG132. Furthermore, tiron had a dramatic protective effect on in vivo lung permeability under mechanical ventilation conditions. Cyclic stretch increased the activation of the NF-κB signaling pathway, which was significantly decreased with the ERK inhibitor U0126. Altogether, our in vitro and in vivo data demonstrate the sensitivity of permeability to stretch- and ventilation-induced superoxide production, suggesting that using antioxidants may be helpful in the prevention and treatment of ventilator-induced lung injury.
journal_name
Am J Respir Cell Mol Biolauthors
Davidovich N,DiPaolo BC,Lawrence GG,Chhour P,Yehya N,Margulies SSdoi
10.1165/rcmb.2012-0252OCsubject
Has Abstractpub_date
2013-07-01 00:00:00pages
156-64issue
1eissn
1044-1549issn
1535-4989pii
rcmb.2012-0252OCjournal_volume
49pub_type
杂志文章abstract::Leukocyte elastase induces apoptosis of lung epithelial cells via alterations in mitochondrial permeability, but the signaling pathways regulating this response remain uncertain. Here we investigated the involvement of proteinase-activated receptor-1 (PAR-1), the transcription factor NF-kappaB, and the protooncogene p...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2008-0157OC
更新日期:2009-12-01 00:00:00
abstract::Increases in inflammatory-cell progenitors have been demonstrated in the bone marrow (BM) after inhalation of Ascaris suum in dogs at the time of allergen-induced airway hyperresponsiveness (AHR). The aim of this study was to evaluate the effect of allergen challenge on trafficking of inflammatory cells and their prog...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb.18.6.3006
更新日期:1998-06-01 00:00:00
abstract::The glucocorticoids (GC) and retinoids (RA) modulate branching morphogenesis and cytodifferentiation in the developing lung. We investigated downstream target genes that link glucocorticoid stimulation to the achievement of a mature lung in glucocorticoid receptor (GR) knockout mice. All GR(null) mice and approximatel...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2002-0047oc
更新日期:2003-01-01 00:00:00
abstract::In allergic airway diseases, intermediate progenitor cells (IPCs) increase in number in the surface epithelium. IPCs arise from basal cells, the origin of hallmark pathological changes, including goblet cell hyperplasia and mucus hypersecretion. Thus, targeting IPCs will benefit future treatment of allergic airway dis...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2020-0350OC
更新日期:2020-12-02 00:00:00
abstract::Enzymes which exhibit core 2 beta1,6 N-acetylglucosaminyltransferase (C2GnT) activity play important roles in physiologic processes including the inflammatory response and immune system function, and C2GnT activity is regulated during processes, such as T cell activation and cellular differentiation. In this study, we...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2002-0147OC
更新日期:2003-07-01 00:00:00
abstract::Increased activity of lung epithelial sodium channels (ENaCs) contributes to the pathophysiology of cystic fibrosis (CF) by increasing the rate of epithelial lining fluid reabsorption. Inter-α-inhibitor (IαI), a serum protease inhibitor, may decrease ENaC activity by preventing its cleavage by serine proteases. High c...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2013-0215OC
更新日期:2014-05-01 00:00:00
abstract::Regulatory T cells (Tregs) play an essential role in maintaining the homeostatic balance of immune responses. Asthma is an inflammatory condition of the airways that is driven by dysregulated immune responses toward normally innocuous antigens. Individuals with asthma have fewer and less functional Tregs, which may le...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章,评审
doi:10.1165/rcmb.2009-0342TR
更新日期:2010-11-01 00:00:00
abstract::In surgically excised nasal polyps, most epithelial mast cells were formalin sensitive, chloroacetate esterase (CAE) negative, and chymase negative. Thus, this represents a population of mast cells not identified by staining for CAE. On the other hand, most stromal mast cells were formalin resistant and CAE positive, ...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb/6.1.37
更新日期:1992-01-01 00:00:00
abstract::Cellular senescence has been implicated in diverse pathologies. However, there is conflicting evidence regarding the role of this process in tissue fibrosis. Although dysregulation of microRNAs is a key mechanism in the pathogenesis of lung fibrosis, it is unclear whether microRNAs function by regulating cellular sene...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2016-0163OC
更新日期:2017-02-01 00:00:00
abstract::The primary function of neutrophils in host defense is to contain and eradicate invading microbial pathogens. This is achieved through a series of swift and highly coordinated responses culminating in ingestion (phagocytosis) and killing of invading microbes. While these tasks are usually performed without injury to h...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章,评审
doi:10.1165/rcmb.2008-0348TR
更新日期:2009-05-01 00:00:00
abstract::Latent cytomegalovirus (CMV) infection is often reactivated in the lung. We postulated that this reactivation could occur by stimulation of the CMV major immediate early (IE) promoter by other viruses that infect the lung. The specific aim of this study was to investigate whether adenovirus early proteins could stimul...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb.10.4.8136160
更新日期:1994-04-01 00:00:00
abstract::Single-cell RNA sequencing (scRNASeq) has advanced our understanding of lung biology, but its utility is limited by the need for fresh samples, loss of cell types by death or inadequate dissociation, and transcriptional stress responses induced during tissue digestion. Single-nucleus RNA sequencing (snRNASeq) has addr...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2020-0095MA
更新日期:2020-12-01 00:00:00
abstract::Congenital diaphragmatic hernia (CDH) is associated with high neonatal mortality from lung hypoplasia and persistent pulmonary hypertension. Pulmonary neuroendocrine cells (PNEC) produce calcitonin gene-related peptide (CGRP), a potent vasodilator. We previously reported altered distribution of CGRP-positive PNEC in f...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb.19.2.2853
更新日期:1998-08-01 00:00:00
abstract::To examine the effects of acid exposure with moderate acidity (pH 3.0-5.0) on bactericidal activity of airway surface liquid (ASL), ASL was collected by washing the surface of primary cultures of human tracheal epithelial cells 24 h after treatment with phosphate-buffered saline (PBS) adjusted to a pH of 3.0, 4.0, or ...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb.26.1.4425
更新日期:2002-01-01 00:00:00
abstract::Hemoglobin (Hb)-based oxygen carriers (HBOCs) are being developed as a potential therapy for increasing tissue oxygenation, yet they have not reached their full potential because of unwanted hemodynamic side effects (vasoconstriction, low cardiac output, and oxygen delivery) due in part to nitric oxide (NO) scavenging...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2008-0364OC
更新日期:2010-02-01 00:00:00
abstract::In this study we examined the effect of oral antigen (Ag) administration on the development of experimental asthma in different mouse strains. We selected BALB/c, BP2, CBA/Ca interleukin (IL)-5 transgenic, and BALB/c T-cell receptor-delta-deficient mouse strains because they exhibit different aspects of the asthma syn...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb.24.5.4320
更新日期:2001-05-01 00:00:00
abstract::Polymorphonuclear neutrophil (PMN) migration across basement membrane is thought to be dependent on the degradation of membrane constituents. PMN gelatinase B, a metalloproteinase able to degrade type IV collagen, may be involved in this phenomenon. PMN gelatinase B is released in the extracellular medium as a latent ...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb.14.3.8845180
更新日期:1996-03-01 00:00:00
abstract::Interleukin (IL)-1beta stimulates the release of granulocyte macrophage colony-stimulating factor (GM-CSF) from lung epithelial cells. To investigate the molecular mechanisms underlying GM-CSF regulation, we studied GM-CSF production, messenger RNA (mRNA) expression levels, and GM-CSF promoter activity in A549 human a...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb.22.5.3889
更新日期:2000-05-01 00:00:00
abstract::Histamine is an important mediator in the pathogenesis of asthma. Variation in genes along the histamine production, response, and degradation pathway may be important in predicting response to antihistamines. We hypothesize that differences exist among single-nucleotide polymorphisms (SNPs) in genes of the histamine ...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2014-0493OC
更新日期:2015-12-01 00:00:00
abstract::We have previously observed that mice exposed to cigarette smoke and treated with exogenous alpha(1)-antitrypsin (A1AT) were protected against the development of emphysema and against smoke-induced increases in serum TNF-alpha. To investigate possible mechanisms behind this latter observation, we cultured alveolar mac...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2006-0345OC
更新日期:2007-08-01 00:00:00
abstract::Polymorphonuclear leukocytes (PMN) and eosinophils (Eos) are important cellular participants in a variety of acute and chronic inflammatory reactions in the airway. Histologic evidence has implicated direct interactions between these two subsets of leukocytes and airway epithelial cells during inflammation. A comprehe...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb.21.3.3478
更新日期:1999-09-01 00:00:00
abstract::T lymphocytes and alveolar macrophages accumulating in the lower respiratory tract of patients with pulmonary sarcoidosis are known to be activated to produce several cytokines, presumably leading to granuloma formation within the lung. We hypothesized that these cells produce colony-stimulating factors (CSFs), which ...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb/3.3.245
更新日期:1990-09-01 00:00:00
abstract::Fibroblasts are the major mesenchymal cells present within the interstitium of the lung and are a major source of vascular endothelial growth factor (VEGF), which modulates the maintenance of pulmonary microvasculature. Prostaglandin E(2) (PGE(2)) acts on a set of E-prostanoid (EP) receptors that activate multiple sig...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2010-0115OC
更新日期:2012-02-01 00:00:00
abstract::Hypervascularity is known as an important element of airway remodeling in bronchial asthma. However, it remains obscure how allergic inflammation relates to angiogenesis in the lung. In this study, we examined the in vitro effects of inflammatory cytokines on endothelial cell functions, particularly angiogenesis. Huma...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2007-0162OC
更新日期:2008-02-01 00:00:00
abstract::Prenatal nicotine exposure impairs normal lung development and leads to diminished pulmonary function after birth. Previous work from our laboratory has demonstrated that nicotine alters lung development by affecting a nonneuronal cholinergic autocrine loop that is expressed in lung. Bronchial epithelial cells (BECs) ...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2008-0352OC
更新日期:2009-07-01 00:00:00
abstract::Persistent polyclonal lymphocytosis has been described in a group of female patients who all have the HLA-DR7 antigen in common and who are all heavy cigarette smokers. Immunoglobulin heavy chain gene rearrangement was analyzed by hybridization with specific immunoglobulin heavy chain genes to restriction enzyme-diges...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb/2.6.549
更新日期:1990-06-01 00:00:00
abstract::Clara cell secretory protein (CCSP), or CC10, is an inhibitor of secretory phospholipase A2 which may be produced by phagocytic cells and by a variety of other cells in the airway. Tumor necrosis factor-alpha (TNF-alpha) is capable of activating phospholipases and inducing the expression of a variety of genes in the a...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb.19.4.3129
更新日期:1998-10-01 00:00:00
abstract::Prior studies have demonstrated that human alveolar macrophages (AM) are suppressive of lymphocyte function, through the mechanism of inhibition is unclear. In the current study, human AM inhibited receptor-mediated increases in intracellular calcium concentration ([Ca2+]i) in T cells, natural killer cells, and B cell...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb/5.5.411
更新日期:1991-11-01 00:00:00
abstract::In the present study, we sought to elucidate the mechanisms by which monocytes migrate into the pleural space in the presence of anaphylatoxins in tuberculous pleural effusion (TPE). Monocytes in both pleural effusion and blood were counted, and their phenotypic characteristics were analyzed. Activation of the complem...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2018-0075OC
更新日期:2019-04-01 00:00:00
abstract::Sufficient pulmonary surfactant production is required for the fetal-neonatal transition, especially in preterm infants. Neuregulin (NRG) and its transmembrane receptor ErbB4 positively regulate the onset of fetal surfactant synthesis. Details of this signaling process remain to be elucidated. ErbB4 is known to regula...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2010-0179OC
更新日期:2011-10-01 00:00:00