Defensins reduce the barrier integrity of a cultured epithelial monolayer without cytotoxicity.

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- and cysteine-rich polypeptides. DEF are bactericidal, fungicidal, viricidal, and tumoricidal, but their ability to contribute to inflammatory injury has not been extensively evaluated. One marker of inflammatory injury is disrupted epithelial barrier integrity. Using Madin-Darby canine kidney (MDCK) epithelial monolayers, we measured the effect of both human and rabbit DEF on barrier integrity using mannitol permeability (Pmann) and transepithelial electrical resistance (Rt). Human DEF (HNP1-3, 2:2:1 molar ratio) increased Pmann in a time- and concentration-dependent manner and Rt fell progressively over a 48-h period after exposure of monolayers to HNP1-3. Rabbit DEF peptide 1 (NP-1) also increased Pmann, but rabbit peptide 5 (NP-5) had no effect on Pmann. To investigate the role of charge, HNP1-3 was added to the monolayers with the polyanions heparin or sulfated dextran. Heparin and sulfated dextran only partially inhibited the increase in Pmann. Fetal bovine serum (FBS), however, completely inhibited the effect of HNP1-3, but this protection was only partially explained by the anionic protein, albumin. The FBS protection was time dependent and was present when FBS was added up to 16 h after exposure to HNP1-3. While both HNP1-3 and NP-1 increased epithelial permeability, neither were cytolytic to MDCK cells as measured by lactate dehydrogenase release.(ABSTRACT TRUNCATED AT 250 WORDS)

authors

Nygaard SD,Ganz T,Peterson MW

doi

10.1165/ajrcmb/8.2.193

subject

Has Abstract

pub_date

1993-02-01 00:00:00

pages

193-200

issue

2

eissn

1044-1549

issn

1535-4989

journal_volume

8

pub_type

杂志文章
  • Cytokines induce an early steroid resistance in airway smooth muscle cells: novel role of interferon regulatory factor-1.

    abstract::We have previously shown that long-term treatment of airway smooth muscle (ASM) cells with a combination of TNF-alpha and IFN-gamma impaired steroid anti-inflammatory action through the up-regulation of glucocorticoid receptor beta isoform (GRbeta) (Mol Pharmacol 2006;69:588-596). We here found that steroid actions co...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2007-0226OC

    authors: Tliba O,Damera G,Banerjee A,Gu S,Baidouri H,Keslacy S,Amrani Y

    更新日期:2008-04-01 00:00:00

  • Metformin enhances cisplatin cytotoxicity by suppressing signal transducer and activator of transcription-3 activity independently of the liver kinase B1-AMP-activated protein kinase pathway.

    abstract::Metformin has been used as first-line treatment in patients with type 2 diabetes, and is reported to reduce cancer risk and progression by activating the liver kinase B1 (LKB1)-AMP-activated protein kinase (AMPK) pathway. Cisplatin remains the main drug for treating advanced non-small-cell lung cancer. However, drug r...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2012-0244OC

    authors: Lin CC,Yeh HH,Huang WL,Yan JJ,Lai WW,Su WP,Chen HH,Su WC

    更新日期:2013-08-01 00:00:00

  • Alpha,beta-unsaturated aldehydes in cigarette smoke release inflammatory mediators from human macrophages.

    abstract::Smoking cigarettes is the major risk factor for chronic obstructive pulmonary disease (COPD). COPD is a condition associated with chronic pulmonary inflammation, characterized by macrophage activation, neutrophil recruitment, and cell injury. Many substances contained in cigarette smoke, including reactive oxygen spec...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2007-0130OC

    authors: Facchinetti F,Amadei F,Geppetti P,Tarantini F,Di Serio C,Dragotto A,Gigli PM,Catinella S,Civelli M,Patacchini R

    更新日期:2007-11-01 00:00:00

  • Pulmonary fibrosis: searching for model answers.

    abstract::Substantial challenges remain in our understanding of fibrotic lung diseases. Nowhere is this more true than in the elucidation and verification of the pathogenetic basis upon which they develop. Scientific progress, most recently in the field of experimental therapy, has relied closely on interpreting data derived fr...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章,评审

    doi:10.1165/rcmb.2005-0062TR

    authors: Chua F,Gauldie J,Laurent GJ

    更新日期:2005-07-01 00:00:00

  • miR-34a Inhibits Lung Fibrosis by Inducing Lung Fibroblast Senescence.

    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

    authors: Cui H,Ge J,Xie N,Banerjee S,Zhou Y,Antony VB,Thannickal VJ,Liu G

    更新日期:2017-02-01 00:00:00

  • Hemolysis-induced Lung Vascular Leakage Contributes to the Development of Pulmonary Hypertension.

    abstract::Although hemolytic anemia-associated pulmonary hypertension (PH) and pulmonary arterial hypertension (PAH) are more common than the prevalence of idiopathic PAH alone, the role of hemolysis in the development of PAH is poorly characterized. We hypothesized that hemolysis independently contributes to PAH pathogenesis v...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2017-0308OC

    authors: Rafikova O,Williams ER,McBride ML,Zemskova M,Srivastava A,Nair V,Desai AA,Langlais PR,Zemskov E,Simon M,Mandarino LJ,Rafikov R

    更新日期:2018-09-01 00:00:00

  • Post-infection A77-1726 blocks pathophysiologic sequelae of respiratory syncytial virus infection.

    abstract::Despite respiratory syncytial virus (RSV) bronchiolitis remaining the most common cause of lower respiratory tract disease in infants worldwide, treatment has progressed little in the past 30 years. The aim of our study was to determine whether post-infection administration of de novo pyrimidine synthesis inhibitors c...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2007-0142OC

    authors: Davis IC,Lazarowski ER,Chen FP,Hickman-Davis JM,Sullender WM,Matalon S

    更新日期:2007-10-01 00:00:00

  • Exogenous nitric oxide enhances neutrophil cell death and DNA fragmentation.

    abstract::Inhaled nitric oxide (NO) is an important new therapeutic agent used to treat pulmonary arterial hypertension in a variety of disease states. However, the effects of NO on cells in the lung are uncertain. Previously, we have shown that NO gas depresses neutrophil oxidative cell function and increases neutrophil cell d...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.18.3.2875

    authors: Fortenberry JD,Owens ML,Brown MR,Atkinson D,Brown LA

    更新日期:1998-03-01 00:00:00

  • Correction of nonsense BMPR2 and SMAD9 mutations by ataluren in pulmonary arterial hypertension.

    abstract::Heritable pulmonary arterial hypertension (HPAH) is a serious lung vascular disease caused by heterozygous mutations in the bone morphogenetic protein (BMP) pathway genes, BMPR2 and SMAD9. One noncanonical function of BMP signaling regulates biogenesis of a subset of microRNAs. We have previously shown that this funct...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2013-0100OC

    authors: Drake KM,Dunmore BJ,McNelly LN,Morrell NW,Aldred MA

    更新日期:2013-09-01 00:00:00

  • IL-5 induces suspended eosinophils to undergo unique global reorganization associated with priming.

    abstract::The experiments described herein define a unique program of polarization of suspended human eosinophils stimulated with IL-5 family cytokines. We found that eosinophil granules and the nucleus move in opposite directions to form, respectively, a granular compartment and the nucleopod, a specialized uropod occupied by ...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2013-0181OC

    authors: Han ST,Mosher DF

    更新日期:2014-03-01 00:00:00

  • Corticosteroids inhibit sphingosine 1-phosphate-induced interleukin-6 secretion from human airway smooth muscle via mitogen-activated protein kinase phosphatase 1-mediated repression of mitogen and stress-activated protein kinase 1.

    abstract::Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid that plays an important proinflammatory role in asthmatic airways. Corticosteroids are first-line antiinflammatories in asthma; however, their repressive effects on S1P-induced cytokine secretion have not been investigated. To address this, our in vitro study r...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2013-0208OC

    authors: Che W,Parmentier J,Seidel P,Manetsch M,Ramsay EE,Alkhouri H,Ge Q,Armour CL,Ammit AJ

    更新日期:2014-02-01 00:00:00

  • Suppression of asthma-like responses in different mouse strains by oral tolerance.

    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

    authors: Russo M,Nahori MA,Lefort J,Gomes E,de Castro Keller A,Rodriguez D,Ribeiro OG,Adriouch S,Gallois V,de Faria AM,Vargaftig BB

    更新日期:2001-05-01 00:00:00

  • Maintenance of airway epithelium in acutely rejected orthotopic vascularized mouse lung transplants.

    abstract::Lung transplantation remains the only therapeutic option for many patients suffering from end-stage pulmonary disease. Long-term success after lung transplantation is severely limited by the development of bronchiolitis obliterans. The murine heterotopic tracheal transplantation model has been widely used for studies ...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2007-0257RC

    authors: Okazaki M,Gelman AE,Tietjens JR,Ibricevic A,Kornfeld CG,Huang HJ,Richardson SB,Lai J,Garbow JR,Patterson GA,Krupnick AS,Brody SL,Kreisel D

    更新日期:2007-12-01 00:00:00

  • Single-Nucleus RNA-Sequencing Profiling of Mouse Lung. Reduced Dissociation Bias and Improved Rare Cell-Type Detection Compared with Single-Cell RNA Sequencing.

    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

    authors: Koenitzer JR,Wu H,Atkinson JJ,Brody SL,Humphreys BD

    更新日期:2020-12-01 00:00:00

  • Competition between elastase and related proteases from human neutrophil for binding to alpha1-protease inhibitor.

    abstract::The protease-antiprotease imbalance that is characteristic of most inflammatory lung disorders depends on the spatial-temporal regulation of active inhibitor and protease concentrations in lung secretions. We have studied the competition between the three main serine proteases from human neutrophil primary granules in...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2004-0374OC

    authors: Korkmaz B,Poutrain P,Hazouard E,de Monte M,Attucci S,Gauthier FL

    更新日期:2005-06-01 00:00:00

  • Serum accelerates the loss of type II cell differentiation in vitro.

    abstract::The differentiated phenotype of the alveolar type II cell is rapidly altered in vitro. To evaluate factors that might influence this process, we isolated and plated rat type II cells in serum-supplemented media to promote adherence and then maintained the cells in a simple nutrient medium in the absence (S- cells) or ...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb/3.4.311

    authors: Paine R 3rd,Joyce-Brady M,Clement A,Brody JS

    更新日期:1990-10-01 00:00:00

  • T cells and lung injury. Impact of rapamycin.

    abstract::Acute lung injury (ALI) is characterized by pulmonary inflammation and edema. Innate immune cells (e.g., neutrophils and macrophages) are major contributors to inflammation in ALI. Less is known regarding the role of T cells. We examined the effects of rapamycin on inflammation in a LPS-induced murine model of ALI. Ra...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2013-0171OC

    authors: Nakajima T,Lin KW,Li J,McGee HS,Kwan JM,Perkins DL,Finn PW

    更新日期:2014-08-01 00:00:00

  • TOLL-interacting Protein in Pulmonary Diseases: Abiding by the Goldilocks Principle.

    abstract::Toll-interacting protein (TOLLIP) is an intracellular adaptor protein with diverse actions throughout the body. In a context- and cell type-specific manner, TOLLIP can function as an inhibitor of inflammation and endoplasmic reticulum stress, an activator of autophagy, or a critical regulator of intracellular vacuole ...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2020-0470TR

    authors: Li X,Goobie GC,Gregory AD,Kass DJ,Zhang Y

    更新日期:2020-11-24 00:00:00

  • Degradation of type IV collagen during the development of fetal rat lung.

    abstract::Lung structure undergoes rapid remodeling during late gestation as a functional respiratory unit is formed. To determine the role of collagen turnover in this process, particularly the basement membrane component, we studied the degradation of collagen in a series of fetal rats from day 18 of gestation to full term. D...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb/9.1.99

    authors: Arden MG,Spearman MA,Adamson IY

    更新日期:1993-07-01 00:00:00

  • Inhaled asbestos fibers induce p53 expression in the rat lung.

    abstract::Humans and rodents exposed to an aerosol of asbestos fibers develop lung injury that can lead to a fibroproliferative response culminating in excessive scarring and impaired lung function. To define the early events that precede asbestos-induced fibrotic lung disease, rats were exposed to an aerosol of chrysotile asbe...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.16.4.9115760

    authors: Mishra A,Liu JY,Brody AR,Morris GF

    更新日期:1997-04-01 00:00:00

  • Suppression of von Hippel-Lindau Protein in Fibroblasts Protects against Bleomycin-Induced Pulmonary Fibrosis.

    abstract::We have reported that von Hippel-Lindau protein (pVHL) expression is elevated in human and mouse fibrotic lungs and that overexpression of pVHL stimulates fibroblast proliferation. We sought to determine whether loss of pVHL in fibroblasts prevents injury and fibrosis in mice that are treated with bleomycin. We genera...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2015-0111OC

    authors: Zhou Q,Chen T,Zhang W,Bozkanat M,Li Y,Xiao L,van Breemen RB,Christman JW,Sznajder JI,Zhou G

    更新日期:2016-05-01 00:00:00

  • Acid stimulation reduces bactericidal activity of surface liquid in cultured human airway epithelial cells.

    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

    authors: Nakayama K,Jia YX,Hirai H,Shinkawa M,Yamaya M,Sekizawa K,Sasaki H

    更新日期:2002-01-01 00:00:00

  • Regulation of lung branching morphogenesis by bombesin-like peptides and neutral endopeptidase.

    abstract::The expression of bombesin-like peptides (BLPs) by pulmonary neuroendocrine cells is transiently upregulated during lung development. A functional role for BLPs is supported by their ability to stimulate lung growth and maturation both in vitro and in vivo during the late stages of lung development. In addition, the c...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.10.6.8003340

    authors: Aguayo SM,Schuyler WE,Murtagh JJ Jr,Roman J

    更新日期:1994-06-01 00:00:00

  • Effects of stress on alveolar macrophages: a role for the sympathetic nervous system.

    abstract::Alveolar macrophages (AMs) play an important role in the regulation of the local immune reactivity in the lung. It was previously shown that exposure of rats to mild inescapable electrical footshock stress (20 min, 4 shocks/min, 5 s/shock, 0.8 mAmp) leads to apparent changes in the activity of AMs upon stimulation, re...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.19.5.3103

    authors: Broug-Holub E,Persoons JH,Schornagel K,Mastbergen SC,Kraal G

    更新日期:1998-11-01 00:00:00

  • Characterization of the effect of interleukin-10 on silica-induced lung fibrosis in mice.

    abstract::We previously described a reduction of silica-induced lung fibrosis in interleukin-10-deficient mice (IL-10-/-) (Huaux and colleagues; Am. J. Respir. Cell Mol. Biol. 1998;18:51-59). In the present study, we further dissect the exact functions of IL-10 in experimental silicosis. The reduced lung fibrotic response to si...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2003-0299OC

    authors: Barbarin V,Arras M,Misson P,Delos M,McGarry B,Phan SH,Lison D,Huaux F

    更新日期:2004-07-01 00:00:00

  • The effect of T-cell depletion on enhanced basophil histamine release after in vitro incubation with live influenza A virus.

    abstract::A number of mechanisms participate in virus-induced asthma. Previously, we described enhanced basophil histamine release (HR) during an experimentally induced rhinovirus infection and after in vitro incubation of peripheral blood mononuclear cells (PBMC) with influenza virus. This study extends our previous observatio...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb/7.4.434

    authors: Huftel MA,Swensen CA,Borcherding WR,Dick EC,Hong R,Kita H,Gleich GJ,Busse WW

    更新日期:1992-10-01 00:00:00

  • IL-13 Augments Compressive Stress-Induced Tissue Factor Expression in Human Airway Epithelial Cells.

    abstract::Tissue factor (TF) is best known as a cellular initiator of coagulation, but it is also a multifunctional protein that has been implicated in multiple pathophysiologic conditions, including asthma. In the lung, airway epithelial cells express TF, but it is unknown how TF expression is regulated by asthma-associated me...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2015-0252OC

    authors: Mitchel JA,Antoniak S,Lee JH,Kim SH,McGill M,Kasahara DI,Randell SH,Israel E,Shore SA,Mackman N,Park JA

    更新日期:2016-04-01 00:00:00

  • Role of stretch on tight junction structure in alveolar epithelial cells.

    abstract::Previous studies have demonstrated that high tidal volumes can cause interstitial and alveolar edema, with degradation of pulmonary epithelial barrier integrity. Separate studies have shown that F-actin disruption and decreased intracellular ATP (ATP(i)) levels in the nonpulmonary epithelium can increase tight junctio...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.25.5.4486

    authors: Cavanaugh KJ Jr,Oswari J,Margulies SS

    更新日期:2001-11-01 00:00:00

  • Modified High-Molecular-Weight Hyaluronan Promotes Allergen-Specific Immune Tolerance.

    abstract::The extracellular matrix in asthmatic lungs contains abundant low-molecular-weight hyaluronan, and this is known to promote antigen presentation and allergic responses. Conversely, high-molecular-weight hyaluronan (HMW-HA), typical of uninflamed tissues, is known to suppress inflammation. We investigated whether HMW-H...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2016-0111OC

    authors: Gebe JA,Yadava K,Ruppert SM,Marshall P,Hill P,Falk BA,Sweere JM,Han H,Kaber G,Harten IA,Medina C,Mikecz K,Ziegler SF,Balaji S,Keswani SG,Perez VA,Butte MJ,Nadeau K,Altemeier WA,Fanger N,Bollyky PL

    更新日期:2017-01-01 00:00:00

  • Asbestos-induced pulmonary fibrosis is augmented in 8-oxoguanine DNA glycosylase knockout mice.

    abstract::Asbestos causes asbestosis and malignancies by mechanisms that are not fully established. Alveolar epithelial cell (AEC) injury and repair are crucial determinants of the fibrogenic potential of noxious agents such as asbestos. We previously showed that mitochondrial reactive oxygen species mediate asbestos-induced AE...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2014-0038OC

    authors: Cheresh P,Morales-Nebreda L,Kim SJ,Yeldandi A,Williams DB,Cheng Y,Mutlu GM,Budinger GR,Ridge K,Schumacker PT,Bohr VA,Kamp DW

    更新日期:2015-01-01 00:00:00