Abstract:
:Specific changes in composition and content of lung extracellular matrix (ECM) proteoglycans (PGs) and hyaluronan (HA) have been observed during the acute response to damage in several forms of injury including infant respiratory distress syndrome (IRDS). These ECM components are thought to modulate the healing response. Hyperoxia, a contributing factor to IRDS, is known to damage both adult and developing lung, however, the extent and pattern of impairment depends on lung maturity. We hypothesized that exposing neonatal rats to hyperoxia alone might result in changes in lung HA, as well as in age-specific changes in lung PGs, similar to those shown to occur in IRDS. In control rats, lung HA decreased over the first 10 days of life, whereas rats exposed to hyperoxia exhibited a time-dependent, time-limited increase in both lung HA and lung wet weight. Histochemistry showed the HA in hyperoxia-exposed lungs to be accumulated in perivascular cuffs of medium sized arteries, and in the alveolar walls. Rats were then exposed to normoxia or hyperoxia for 7 days beginning at either 3 days of life (neonatal) or 21 days (adolescent), and lung tissue was cultured in the presence of [35S]-sulfate to label newly synthesized PGs. Proteoglycans were extracted, and analyzed by isopycnic CsCl gradient centrifugation, sequential enzymatic deglycosylation, size chromatography, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). When controlled for total protein extracted, 63% more label was incorporated into large molecular weight material in the tissue exposed to hyperoxia, with a 95% increase in incorporation in the most dense fraction, D1. [35S]-Sulfate incorporation into chondroitin and dermatan sulfate in hyperoxic tissue specifically increased 116% (242% in the D1 fraction), while incorporation into heparan sulfate remained essentially unchanged. There was a nearly fivefold increase in [35S]-sulfate incorporation into chondroitin sulfate chains in the D1 fraction. When the D1 fractions of extracts of treated and control rat lungs were compared on SDS-PAGE, a large chondroitin sulfate proteoglycan (CSPG; core protein of 195 kDa) was upregulated in the D1 fraction from hyperoxic tissue of neonatal rats, but was not detected in the lungs of adolescent animals exposed to hyperoxia. This CSPG and four additional large CSPGs were noted to be upregulated on western blotting by a polyclonal antibody directed against the G1 domain of the aggrecan protein core. We conclude that hyperoxia alone causes an increase in lung HA and lung water, and speculate that this contributes significantly to the clinical syndrome of IRDS. In addition, several large CSPGs are upregulated by hyperoxic exposure in a developmentally specific manner. We speculate that this increase in CSPGs may interfere with the normal developmental sequence of events, contributing to hypoalveolarization.
journal_name
Am J Respir Cell Mol Biolauthors
Juul SE,Krueger RC Jr,Scofield L,Hershenson MB,Schwartz NBdoi
10.1165/ajrcmb.13.6.7576700subject
Has Abstractpub_date
1995-12-01 00:00:00pages
629-38issue
6eissn
1044-1549issn
1535-4989journal_volume
13pub_type
杂志文章abstract::We have determined eicosanoid production from endogenous arachidonic acid by neonatal lamb lungs stimulated with calcium ionophore A23187 during normoxia and hypoxia. Lungs of lambs 19 to 25 d of age were isolated and perfused with cell-free Krebs' bicarbonate buffer at a flow rate of 15 to 20 ml/kg/min. After 30 min ...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb/4.4.379
更新日期:1991-04-01 00:00:00
abstract::The time course and nature of the cellular response to left pneumonectomy, with or without prior adrenalectomy, were evaluated in the right lungs of male Sprague-Dawley rats using morphometric techniques. Animals were studied at days 2, 5, and 14 following pneumonectomy, intervals prior to, during the course of, and f...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb/5.4.351
更新日期:1991-10-01 00:00:00
abstract::The cells/proteases responsible for the development of smoke-induced emphysema is an area of intense investigation. Mice with knockout of macrophage metalloelastase genes (MME(-/-)) do not develop emphysema after smoke exposure, but we also observed that neutrophils (PMN) in lavage appeared to be a requirement for acu...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.4791
更新日期:2002-09-01 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::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::Endothelin-1 is a potent bronchoconstrictor peptide with pro-inflammatory and growth-promoting properties. After exposure of sensitized Brown-Norway rats to six repeated ovalbumin exposures, there was an increase in pro-endothelin (ET)-1 messenger RNA compared with saline-exposed control rats 24 h after the final expo...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb.23.5.3909
更新日期:2000-11-01 00:00:00
abstract::Airway epithelial cells can respond to infection by activating several signaling pathways. We examined the induction of apoptosis in response to Pseudomonas aeruginosa PAO1 in normal cells and several cystic fibrosis (CF) and corrected cell lines. Epithelial cells in monolayers with tight junctions, confirmed by apica...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb.23.3.4098
更新日期:2000-09-01 00:00:00
abstract::Surfactant is an apically-secreted surface-active material containing primarily disaturated phosphatidylcholine (DSPtdCho) that is released from alveolar epithelia into the alveolus. Surfactant deficiency is an important aspect of inflammatory lung disease and may result from extravasation of serum lipoproteins into t...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2004-0038OC
更新日期:2004-08-01 00:00:00
abstract::Cigarette smoking is a major risk factor for chronic obstructive pulmonary disease (COPD). Recent reports of increased matrix metalloproteinase-2 (MMP-2) in lungs of patients with emphysema support the paradigm of proteinase/antiproteinase imbalance in the pathogenesis of COPD. We sought to define the signaling pathwa...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2006-0106OC
更新日期:2007-04-01 00:00:00
abstract::A defining feature of acute lung injury (ALI) is the increased lung vascular permeability and alveolar flooding, which leads to associated morbidity and mortality. Specific therapies to alleviate the unremitting vascular leak in ALI are not currently clinically available; however, our prior studies indicate a protecti...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2010-0422OC
更新日期:2011-08-01 00:00:00
abstract::Surfactant protein (SP)-D, a 43-kD multifunctional collagen-like lectin, is synthesized and secreted by the airway epithelium. SP-D knockout (SP-D [-/-]) mice exhibit an increase in the number and size of airway macrophages, peribronchiolar inflammation, increases in metalloproteinase activity, and development of emph...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2003-0091OC
更新日期:2004-03-01 00:00:00
abstract::Enhanced airway smooth muscle (ASM) contractility contributes to increased resistance to airflow in diseases such as bronchitis and asthma that occur in passive smokers exposed to secondhand smoke. Little information exists on the cellular mechanisms underlying such airway hyperreactivity. Sputum samples of patients w...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 临床试验,杂志文章
doi:10.1165/rcmb.2012-0129OC
更新日期:2013-04-01 00:00:00
abstract::5-oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE) is a metabolite of arachidonic acid formed by the oxidation of 5-hydroxy-6,8,11, 14-eicosatetraenoic acid by a highly specific dehydrogenase. 5-oxo-ETE is a chemoattractant for both neutrophils and eosinophils. Although it is not as effective as leukotriene B4 (LTB4) a...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb.20.1.3141
更新日期:1999-01-01 00:00:00
abstract::Primary pulmonary hypertension is characterized by increased pulmonary vascular resistance and smooth muscle proliferation. Stable analogs are increasingly being used to treat this disease, although no data exists comparing their effects on proliferation. We therefore investigated the antiproliferative activity of sev...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb.26.2.4695
更新日期:2002-02-01 00:00:00
abstract::We investigated the effects of hypoxia (< 2.5% O2) on rat manganese superoxide dismutase (MnSOD) gene promoter-luciferase reporter constructs in transiently transfected lung epithelial cells (A549, L2, and E1A-T2) and fibroblasts (R9Ab). We cloned MnSOD promoter-luciferase reporter constructs (numbers refer to length ...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb.21.1.3521
更新日期:1999-07-01 00:00:00
abstract::We sought to determine whether an intact bone marrow is essential to lung repair following bleomycin-induced lung injury in mice, and the mechanisms of any protective effects conferred by bone marrow-derived mesenchymal stem cell (BMDMSC) transfer. We found that myelosupression increased susceptibility to bleomycin in...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2004-0330OC
更新日期:2005-08-01 00:00:00
abstract::Polymorphonuclear leukocytes (PMN) contribute to epithelial injury at sites of inflammation, but their mechanisms of action are incompletely understood. PMN can injure target tissues by oxidative and nonoxidative mechanisms. Included in the nonoxidative mechanisms are defensins (DEF), small (3.5 to 4.0 kD), arginine- ...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb/8.2.193
更新日期:1993-02-01 00:00:00
abstract::The doxycycline-inducible, gene regulatory system allows tight control of transgene expression for the study of organ development and disease pathogenesis. Multiple recent reports have employed this model to investigate various lung diseases including emphysema. For our study, we used this transgenic system to test wh...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2005-0378OC
更新日期:2006-05-01 00:00:00
abstract::To identify relationships amongst tracheal and alveolar epithelial cells during lung development, we used conditional systems controlled by the rat CCSP and human SFTPC gene promoters to express Cre-recombinase in the developing mouse lung, thereby permanently labeling cells by expression of alkaline phosphatase or gr...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2005-0180OC
更新日期:2005-11-01 00:00:00
abstract::To evaluate the response of an epithelial barrier to a moderate but sustained oxidative stress, we cultured monolayers of Madin Darby canine kidney cells on microporous filters and exposed them to the hypoxanthine-xanthine oxidase (HX-XO) reaction. The transepithelial permeability coefficient for mannitol (Pm) was ass...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb/9.5.496
更新日期:1993-11-01 00:00:00
abstract::Although neuroanatomical and neurophysiological features of neurons in the ferret trachea have been studied, the neural mediators associated with this plexus have not been completely characterized. The purpose of this study was to examine the occurrence of choline acetyltransferase (ChAT), nitric oxide synthase (NOS),...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb.14.3.8845170
更新日期:1996-03-01 00:00:00
abstract::Sox2, a transcription factor critical for the maintenance of embryonic stem cells and induction of pluripotent stem cells, is expressed exclusively in the conducting airway epithelium of the lung, where it is required for differentiation of nonciliated, goblet, and ciliated cells. To determine the role of Sox2 in resp...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2010-0149OC
更新日期:2011-07-01 00:00:00
abstract::DNA double-strand breaks (DSBs) can result in cell death or genetic alterations when cells are subjected to radiation, exposure to toxins, or other environmental stresses. A complex DNA-damage-response pathway is activated to repair the damage, and the inability to repair these breaks can lead to carcinogenesis. One o...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2009-0062OC
更新日期:2010-08-01 00:00:00
abstract::IL-13 is a T-helper class 2 cytokine that induces goblet cell hyperplasia and mucus production in airway epithelial cells. Because macrolide antibiotics are known to have immunomodulatory and mucoregulatory properties, the aim of this study was to examine the effect of clarithromycin on IL-13-induced goblet cell hyper...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2010-0327OC
更新日期:2011-11-01 00:00:00
abstract::Identification of the genetic loci underlying asthma in humans has been hampered by variability in clinical phenotype, uncontrolled environmental influences, and genetic heterogeneity. To circumvent these complications, the genetic regulation of asthma-associated phenotypes was studied in a murine model. We characteri...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb.23.4.4199
更新日期:2000-10-01 00:00:00
abstract::Accumulating evidence has demonstrated that up-regulation of the angiotensin (Ang)-converting enzyme (ACE)/AngII/AngII type 1 receptor (AT1R) axis aggravates pulmonary fibrosis. The recently discovered ACE2/Ang-(1-7)/Mas axis, which counteracts the activity of the ACE/AngII/AT1R axis, has been shown to protect against...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2012-0451OC
更新日期:2014-04-01 00:00:00
abstract::Previous work demonstrated that pre-exposure to ozone primes innate immunity and increases Toll-like receptor-4 (TLR4)-mediated responses to subsequent stimulation with LPS. To explore the pulmonary innate immune response to ozone exposure further, we investigated the effects of ozone in combination with Pam3CYS, a sy...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2012-0187OC
更新日期:2013-01-01 00:00:00
abstract::Alveolar epithelial type II cells secrete lung surfactant via exocytosis. Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNARE) are implicated in this process. Lipid rafts, the cholesterol- and sphingolipid-rich microdomains, may offer a platform for protein organization on the cell membrane. ...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2005-0418OC
更新日期:2006-06-01 00:00:00
abstract::Increased susceptibility to infections, including tuberculosis (TB), is a major cause of morbidity and mortality in patients with diabetes. Despite the clinical importance of this problem, little is known about how diabetes impairs protective immunity. We modeled this phenomenon by infecting acute (< or = 1 mo) or chr...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2006-0478OC
更新日期:2007-11-01 00:00:00
abstract::Distribution of actin and fodrin, a nonerythroid analogue of spectrin, was studied in cytocentrifuge preparations and in tissue sections of normal and pathologic respiratory epithelium by using immunofluorescence and immunoelectron microscopy. In ciliated epithelial cells and in goblet cells of normal bronchial epithe...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb.11.1.8018340
更新日期:1994-07-01 00:00:00