Cigarette smoking is a risk factor for several lung diseases, including chronic obstructive pulmonary disease, cardiovascular disease and lung cancer. The potential health effects of chronic use of electronic nicotine delivery systems (ENDS) is unclear. This study utilized fully differentiated primary normal human bronchial epithelial (NHBE) cultures in a repeat-dose exposure to evaluate and compare

Rats are often used in ventilator-induced lung injury (VILI) models. However, strain-specific susceptibility for VILI has not been elucidated yet. The aim of this study was to demonstrate strain-specific differences in VILI in infant Sprague Dawley and Wistar rats. VILI was compared in two week old pups after 8 hours of protective or injurious ventilation. Pups were ventilated with tidal volumes (VT)

Lung development is a complicated and delicate process, facilitated by spatially and temporarily coordinated crosstalk of up to 40 cell types. Developmental origin and heterogeneity of lung cell lineages in context of lung development have been a focus of research efforts for decades. Bulk RNA and protein measurements, RNA and protein labelling, and lineage tracing techniques have been traditionally

Lungs of smokers and COPD are severely compromised and are susceptible to SARS-CoV-2 attack. The lethal combination of enhanced SARS-CoV-2 attachment receptor protein ACE2 along with an increase in endocytic vacuoles will enable viral attachment, entry, and replication. The objective of the study was to identify the presence of SARS-CoV-2 host attachment receptor angiotensin-converting enzyme-2 (ACE2)

Background: The COVID-19 pandemic is an ongoing threat to public health. Since the identification of COVID-19, the disease caused by SARS-CoV-2, no drugs have been developed to specifically target SARS-CoV-2. To develop effective and safe treatment options, a better understanding of cellular mechanisms underlying SARS-CoV-2 infection is required. To fill this knowledge gap, researchers require reliable

Chronic obstructive pulmonary disease (COPD) is characterized by the destruction of alveolar tissue (in emphysema) and airway remodeling (leading to chronic bronchitis) which cause difficulties in breathing. It is a growing public health concern with few therapeutic options that can reverse disease progression or mortality. This is in part because current treatments mainly focus on ameliorating symptoms

Platelet-derived growth factor receptor alpha (PDGFRα) is absolutely required for the development of secondary pulmonary alveolar septa. Our earlier observations indicated that PDGFRα resides intracellularly as well as on the plasma membrane of murine lung fibroblasts (LF). We have examined how neuropilin-1 (Nrp1), a surface receptor without kinase activity, regulates the intracellular trafficking

Aims: Postoperative pulmonary complications including acute lung injury (ALI) and acute respiratory distress syndrome have contributed to the mortality and morbidity of orthotopic liver transplantation (OLT) with unclear mechanisms. Mast cells (MCs) and polymorphonuclear neutrophils (PMNs) are the main inflammatory cells and participants in the process of ALI. The present study was designed to investigate

The objective of this study was to determine the effect of pulmonary intravascular macrophage depletion on systemic inflammation and ex vivo neutrophil apoptosis, using an experimental model of intestinal ischemia and reperfusion injury in horses. Neutrophils were isolated before and after surgery from horses that were randomized to 3 treatment groups: sham celiotomy (CEL, n=4), intestinal ischemia

Background. Microvesicles (MVs) released from almost all cells are recognized as cell communication tools. MVs have been investigated in several inflammatory diseases but poorly in biological fluids like bronchoalveolar lavage (BAL) of smokers. Aims. The purpose of this study was to investigate the presence and source of MVs in BAL of smokers with and without COPD compared to non-smoking controls.

Coronavirus disease 2019 (COVID-19), driven by SARS-CoV-2, is now declared a global pandemic. Pathogenic T cells and inflammatory monocytes are regarded as the central drivers of the cytokine storm associated with the severity of COVID-19. In this study, we explored the characteristic peripheral cellular profiles of patients with COVID-19 in both acute and convalescent phases by single-cell mass cytometry

In human airway smooth muscle (hASM), mitochondrial volume density is greater in asthmatic patients compared to normal controls. There is also an increase in mitochondrial fragmentation in hASM of moderate asthmatics associated with an increase in Drp1 and a decrease in Mfn2 expression, mitochondrial fission and fusion proteins, respectively. Pro-inflammatory cytokines such TNFα contribute to hASM

Despite advances in the pathophysiology of Chronic Obstructive Pulmonary Disease (COPD), there is a distinct lack of biochemical markers to aid clinical management. Microvesicles (MVs) have been implicated in the pathophysiology of inflammatory diseases including COPD but their association to COPD disease severity remains unknown. We analysed different MV populations in plasma and bronchoalveolar lavage

The COVID-19 pandemic is associated with severe pneumonia and acute respiratory distress syndrome leading to death in susceptible individuals. For those who recover, post-COVID-19 complications may include development of pulmonary fibrosis. Factors contributing to disease severity or development of complications is not known. Using computational analysis with experimental data, we report that IPF and

Precision-cut lung slices (PCLS) have gained increasing interest as a model to study lung biology/disease and screening novel therapeutics. In particular, PCLS derived from human tissue can better recapitulate some aspects of lung biology/disease as compared to animal models. Several experimental readouts have been established for use with PCLS, but obtaining high yield and quality RNA for downstream

Premature infants, especially those with bronchopulmonary dysplasia (BPD), develop recurrent severe respiratory viral illnesses. We have shown that hyperoxic exposure of immature mice, a model of BPD, increases lung IL-12-producing Clec9a+CD103+ dendritic cells (DCs), pro-inflammatory responses and airway hyperreactivity following rhinovirus (RV) infection. However, the requirement for CD103+ DCs and

Tobacco smoke has harmful effects on a multi-organ level. Exposure to smoke, whether in utero or environmental, significantly increases susceptibility. This susceptibility has been identified to be divergent between males and females. However, there remains a distinct lack of thorough research into the relationship between sex and exposure to tobacco. Females tend to generate a more significant response

American Journal of Physiology-Lung Cellular and Molecular Physiology, Ahead of Print.

American Journal of Physiology-Lung Cellular and Molecular Physiology, Ahead of Print.

American Journal of Physiology-Lung Cellular and Molecular Physiology, Ahead of Print.

American Journal of Physiology-Lung Cellular and Molecular Physiology, Ahead of Print.

American Journal of Physiology-Lung Cellular and Molecular Physiology, Ahead of Print.

Oxygen is the most commonly used therapy in hospitalized patients with COVID-19. In those patients who develop worsening pneumonia and acute respiratory distress syndrome (ARDS), high concentrations of oxygen may need to be administered for prolonged time periods, often together with mechanical ventilation. Hyperoxia, although lifesaving and essential for maintaining adequate oxygenation in the short-term

In this study, a genetically diverse panel of 43 mouse strains was exposed to ammonia and genome-wide association mapping was performed employing a single nucleotide polymorphism (SNP) assembly. Transcriptomic analysis was used to help resolve the genetic determinants of ammonia-induced acute lung injury. The encoded proteins were prioritize based on molecular function, nonsynonymous SNP within a functional

Rationale:Acute respiratory distress syndrome (ARDS) is characterized by pulmonary edema and poor gas exchange resulting from severe inflammatory lung injury. Neutrophilic infiltration and increased pulmonary vascular permeability are hallmarks of early ARDS and precipitate a self-perpetuating cascade of inflammatory signaling. The biochemical processes initiating these events remain unclear. Typically

Ozone is known to cause lung injury and resident cells of the respiratory tract, i.e., epithelial cells and macrophages, respond to inhaled ozone in a variety of ways that affect their survival, morphology, and functioning. However, a complete understanding of the sex-associated and the cell type-specific gene expression changes in response to ozone exposure is still limited. Through transcriptomics

Pulmonary fibrosis is one of the important causes of morbidity and mortality in fibroproliferative disorders such as systemic sclerosis (SSc) and idiopathic pulmonary fibrosis (IPF). Lysyl oxidase (LOX) is a copper-dependent amine oxidase whose primary function is the covalent crosslinking of collagens in the extracellular matrix (ECM). We investigated the role of LOX in the pathophysiology of SSc

Background: Oxidative stress caused by mechanical ventilation contributes to the pathophysiology of ventilator-induced lung injury (VILI). A key mechanism maintaining redox balance is the up-regulation of Nrf2-dependent antioxidant gene expression. We tested whether pretreatment with a Nrf2-ARE pathway activator tert-butylhydroquinone (tBHQ) protects against VILI. Methods: Male C57BL/6J mice were pretreated

American Journal of Physiology-Lung Cellular and Molecular Physiology, Volume 319, Issue 4, Page L752-L753, October 2020.

American Journal of Physiology-Lung Cellular and Molecular Physiology, Ahead of Print.

American Journal of Physiology-Lung Cellular and Molecular Physiology, Ahead of Print.

Chronic hypoxia (CH)-induced pulmonary hypertension (PH) results, in part, from TH17 cell-mediated perivascular inflammation. However, the antigen/s involved are unknown. Cellular immunity to collagen type V (col V) develops after ischemia-reperfusion injury during lung transplant and is mediated by naturally occurring "nTH17" cells. COL5A1 codifies for the α1 helix of col V, which is normally hidden

American Journal of Physiology-Lung Cellular and Molecular Physiology, Ahead of Print.

The incidence, severity and mortality of ongoing coronavirus infectious disease-19 (COVID-19) is greater in men compared to women, but the underlying factors contributing to this sex difference are still being explored. In the current study, using primary isolated human airway smooth muscle (ASM) cells from normal males vs. females as a model, we explored the effect of estrogen vs. testosterone in

For patients with end-stage lung disease, lung transplantation is a lifesaving therapy. Currently however, the number of patients which require a transplant exceed the number of donor lungs available. One of the contributing factors to this is the conservative mindset of physicians whom are concerned about transplanting marginal lungs due to the potential risk of primary graft dysfunction. Ex vivo

Primary ciliary dyskinesia (PCD) is an inherited disorder of the motile cilia. Early accurate diagnosis is important to help prevent lung damage in childhood and to preserve lung function. Confirmation of a diagnosis traditionally relied on assessment of ciliary ultrastructure by transmission electron microscopy (TEM), however >40 known PCD genes has made the identification of bi-allelic mutations

The COVID-19 pandemic has reached most of the countries worldwide causing death, which often results from an inflammatory storm associated with severe acute respiratory syndrome (SARS). This has prompted researchers to seek specific novel and definitive treatments urgently. In this context, it is interesting to evaluate the preventive and therapeutic effects of existing pharmacological agents that

Electronic nicotine delivery systems, or e.cigarettes utilise a liquid solution that normally contains propylene glycol (PG) and vegetable glycerine (VG) to generate vapour and act as a carrier for nicotine and flavourings. Evidence indicated these 'carriers' reduced growth and survival of epithelial cells including those of the airway. We hypothesised that 3% PG or PG mixed with VG (3% PG:VG, 55:45)

Inhalation of organic dust is an occupational hazard leading to the development of respiratory symptoms and respiratory diseases. Bioaerosols from concentrated animal feeding operations are rich in bacteria and could carry bacterial extracellular vesicles (EVs) that could induce lung inflammation. It is not known if organic dust contains bacterial EVs and whether they modulate lung inflammation. Herein

American Journal of Physiology-Lung Cellular and Molecular Physiology, Ahead of Print.

American Journal of Physiology-Lung Cellular and Molecular Physiology, Ahead of Print.

Background: Phenylalanine levels are associated with pulmonary hypertension in metabolic profiling clinical studies. However, the pathophysiologic role of phenylalanine on pulmonary circulation is still unclear. We experimentally addressed the direct impact of phenylalanine on pulmonary circulation in rats and explored the underlying molecular pathway. Methods and results: Phenylalanine was injected

S100 calcium-binding protein A9 (S100A9), is elevated in plasma and bronchoalveolar lavage fluid (BALF) of COPD patients and aging enhances S100A9 expression in several tissues. Currently, the direct impact of S100A9-mediated signaling on lung function and within the aging lung is unknown. Here, we observed that elevated S100A9 levels in human BALF correlated with age. Elevated lung levels of S100A9

The gasotransmitter carbon monoxide (CO) regulates fluid and electrolyte movements across epithelial tissues. However, its action on anion channels is incompletely understood. Here, we investigate the direct action of CO on the cystic fibrosis transmembrane conductance regulator (CFTR) by applying CO-releasing molecules (CORMs) to the intracellular side of excised inside-out membrane patches from cells

American Journal of Physiology-Lung Cellular and Molecular Physiology, Ahead of Print.

The cellular communication network factor 1 (CCN1) is a matricellular protein that can modulate multiple tissue responses including inflammation and repair. We have previously shown that adenoviral overexpression of Ccn1 is sufficient to cause acute lung injury in mice. We hypothesized that CCN1 is present in the airspaces of lungs during the acute phase of lung injury and higher concentrations are

The recurrent emergence of novel, pathogenic coronaviruses (CoVs) SARS-CoV-1 (2002), MERS-CoV (2012) and most recently SARS-CoV-2 (2019) has highlighted the need for physiologically informative airway epithelial cell infection models for studying immunity to CoVs and development of anti-viral therapies. To address this, we developed an in-vitro infection model for two human coronaviruses; alphacoronavirus

Anti-retroviral therapy in HIV patients has lengthened life span but led to an increased risk for secondary co-morbidities, such as pulmonary complications characterized by vascular dysfunction. In the lung, PDGFRb+ mesenchymal cells known as pericytes intimately associate with endothelial cells and are key for their survival, both structurally and through the secretion of pro-survival factors. We

Growing evidence demonstrates that human mesenchymal stromal cells (MSCs) modify their in vivo anti-inflammatory actions depending on the specific inflammatory environment encountered. Understanding this better is crucial to refine MSC-based cell therapies for lung and other diseases. Using acute exacerbations of cystic fibrosis (CF) lung disease as a model, the effects of ex vivo MSC exposure to clinical

Recent clinical trials have shown improvements in neonatal outcomes after intratracheal administration of combination budesonide/surfactant (ITBS)in infants at risk of bronchopulmonary dysplasia. However, the effect of ITBSon lung function and alveolar structure is not known. We aimed to determine the effect of ITBSon lung function, parenchymal structure and inflammatory cytokine expression in a relevant

Airway smooth muscle hyperresponsiveness associated with chronic airway inflammation leads to the typical symptoms of asthma including bronchoconstriction and wheezing. Asthma severity is associated with airway inflammation; therefore reducing airway inflammation is an important therapeutic target. Gelsolin is an actin capping and severing protein that has been reported to be involved in modulation

Bronchopulmonary dysplasia (BPD)-associated pulmonary hypertension (PH) is a chronic infantile lung disease that lacks curative therapies. Infants with BPD-associated PH are often exposed to hyperoxia and additional insults such as sepsis that contribute to disease pathogenesis. Animal models that simulate these scenarios are necessary to develop effective therapies; therefore, we investigated whether

Airway epithelial homeostasis is under constant threat due to continuous exposure to the external environment, and abnormally robust sensitivity to external stimuli is critical to the development of airway diseases, including asthma. Ku is a key non-homologous end-joining DNA repair protein with diverse cellular functions such as VDJ recombination and telomere length maintenance. Here we show a novel

A rapidly expanding new field of lung research has been produced by the emergence of culture-independent next-generation sequencing technologies. While pulmonary microbiome research lags behind the exploration of the microbiome in other organ systems, the field is maturing and has recently produced multiple exciting discoveries. In this Mini-Review, we will explore recent advances in our understanding

The severity of coronavirus disease 2019 (COVID-19) is linked to an increasing number of risk factors, including exogenous (environmental) stimuli such as air pollution, nicotine, and cigarette smoke. These three factors increase the expression of angiotensin I converting enzyme 2 (ACE2), a key receptor involved in the entry of SARS-CoV-2 -the etiological agent of COVID-19- into respiratory tract epithelial

Bronchomotor tone is regulated by contraction and relaxation of airway smooth muscle (ASM). A weakened ASM relaxation might be a cause of the airway hyperresponsiveness, a characteristic feature of bronchial asthma. Pituitary adenylyl cyclase-activating polypeptide (PACAP) is known as a mediator that causes ASM relaxation. To date, whether or not the PACAP responsiveness is changed in asthmatic ASM

G551D is a major disease-associated gating mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) protein, an ATP- and phosphorylation-dependent chloride channel. G551D causes severe CF disease by disrupting ATP-dependent channel opening, however, whether G551D affects phosphorylation-dependent channel activation is unclear. Here, we use macro patch recording and Ussing chamber

Mucosal surfaces are constantly exposed to a microbiome consisting of micro-organisms that heavily influence human immunity and health. In the lung these micro-organisms consist of bacteria, viruses and fungi and exist in a relatively low biomass state. Bacterial communities of the lung modulate local inflammation and correlate with changes in pulmonary physiology and clinical outcomes in patients

The molecular mechanisms underlying pulmonary arterial hypertension (PAH) in congenital ventricular septal defects (VSD) are unclear. We aimed to reveal molecular pathways and potential biomarkers by multi-omics analysis in VSD-PAH. Plasma from 160 children, including 120 VSD patients with/without PAH and 40 healthy children was studied by integrated proteomics, metabolomics, and bioinformatics analyses

Morbidity and mortality rates in acute lung injury (ALI) increase with age. Since alveolar epithelial type II cells (AE2) are crucial for lung function and repair, we hypothesized that aging promotes senescence in AE2 and contributes to the severity and impaired regeneration in ALI. ALI was induced with 2.5 μg lipopolysaccharide/g body weight in young (3 months) and old (18 months) mice that were sacrificed