American Journal of Respiratory Cell and Molecular Biology

Lung inflammation, caused by acute exposure to ozone (O3 ) - one of the six criteria air pollutants - is a significant source of morbidity in susceptible individuals. Alveolar macrophages (AMØs) are the most abundant immune cells in the normal lung and their number increases following O3 exposure. However, the role of AMØs in promoting or limiting O3 -induced lung inflammation has not been clearly defined. Here, we used a mouse model of acute O3 exposure, lineage tracing, genetic knockouts, and data from O3 -exposed human volunteers to define the role and ontogeny of AMØs during acute O3 exposure...

Small muscular pulmonary artery remodeling is a dominant feature of PAH. PSEN1 affects angiogenesis, cancer and Alzheimer's disease. We aimed to determine the role of PSEN1 in the pathogenesis of vascular remodeling in PH. Haemodynamics and vascular remodeling in the Psen1 -knockin and smooth muscle-specific Psen1 -knockout mice were assessed. The functional partners of PSEN1 were predicted by bioinformatics analysis and biochemical experiments. The therapeutic effect of PH was evaluated by administration of the PSEN1-specific inhibitor ELN318463...

Cigarette smoking is known to be the leading cause of chronic obstructive pulmonary disease (COPD). However, the detailed mechanisms have not been elucidated. Platelet-activating factor (PAF), a potent inflammatory mediator, is involved in the pathogenesis of various respiratory diseases, such as bronchial asthma or COPD. We focused on lysophospholipid acyltransferase 9 (LPLAT9), a biosynthetic enzyme of PAF, in the pathogenesis of COPD. LPLAT9 gene expression was observed in excised COPD lungs and single-cell RNA sequencing data of alveolar macrophage (AM)...

No abstract text is available yet for this article.

No abstract text is available yet for this article.

The recent European Respiratory Society statement on familial pulmonary fibrosis (FPF) supports the need of genetic testing in the care of patients and their relatives. However, no solution (i.e., a concrete test) was provided to implemented genetic testing in daily practice. Herein, we tabulated and standardized the nomenclature of 128 genetic variants in 20 genes implicated in adult-onset pulmonary fibrosis. The objective was to develop a laboratory developed test (LDT) based on standard Sanger sequencing in order to capture all known FPF-associated variants...

No abstract text is available yet for this article.

No abstract text is available yet for this article.

Sepsis is a systemic inflammatory response that requires effective macrophage metabolic functions to resolve ongoing inflammation. Previous work showed that the mechanosensitive cation channel, transient receptor potential vanilloid 4 (TRPV4), mediates macrophage phagocytosis and cytokine production in response to lung infection. Here, we show that TRPV4 regulates glycolysis in a stiffness dependent manner by augmenting macrophage glucose uptake by GLUT1. In addition, TRPV4 is required for lipopolysaccharide (LPS)-induced phagolysosome maturation in a GLUT1-dependent manner...

Lung macrophages constitute a sophisticated surveillance and defense system that contributes to tissue homeostasis, host defense, and allows the host to cope with the myriad of insults and antigens to which the lung mucosa is exposed. As opposed to alveolar macrophages, lung interstitial macrophages express high levels of type 2 major histocompatibility complex (MHC-II), a hallmark of antigen-presenting cells. Here, we showed that lung IMs, like dendritic cells (DCs), possess the machinery to present soluble antigens in an MHC-II-restricted way...

Severe viral lower respiratory tract infection (LRTI), resulting in both acute and long-term pulmonary disease, constitutes a substantial burden among young children. Viral LRTI triggers local oxidative stress pathways by infection and inflammation, and supportive care in the pediatric intensive care unit may further aggravate oxidative injury. The main goal of this exploratory study was to identify and monitor breath markers linked to oxidative stress in children over the disease course of severe viral LRTI...

The role of alternative splicing in Chronic Obstructive Pulmonary Disease (COPD) is still largely unknown. We aimed to investigate the differences in alternatively splicing events between patients with mild-to-moderate and severe COPD compared to non-COPD controls and to identify splicing factors associated with aberrant alternative splicing in COPD. For this purpose, we performed genome-wide RNA-seq analysis of bronchial brushings from 23 mild-to-moderate, 121 severe COPD patients, and 23 non-COPD controls...

Newborns with intrauterine growth restriction (IUGR) have a higher likelihood of developing pulmonary arterial hypertension (PAH) in adulthood. While there is increasing evidence suggesting that pericytes play a role in regulating myofibroblast transdifferentiation and angiogenesis in malignant and cardiovascular diseases, their involvement in the pathogenesis of IUGR-related PH and the underlying mechanisms remain incompletely understood. To address this issue, a study was conducted utilizing a Sprague-Dawley (SD) rat model of IUGR-related PH...

No abstract text is available yet for this article.

No abstract text is available yet for this article.

Growth differentiation factor 15 (GDF15) is a stress cytokine with several proposed roles including support of stress erythropoiesis. Higher circulating GDF15 levels are prognostic of mortality during acute respiratory distress syndrome, but the cellular sources and downstream effects of GDF15 during pathogen-mediated lung injury are unclear. We quantified GDF15 in lower respiratory tract biospecimens and plasma from patients with acute respiratory failure. Publicly available data from SARS-CoV-2 infection were re-analyzed...

Various infections trigger a storm of pro-inflammatory cytokines, in which IL-6 acts as a major contributor and leads to diffuse alveolar damage in patients. However, the metabolic regulatory mechanisms of IL-6 in lung injury remain unclear. Polyriboinosinic-polyribocytidylic acid (poly(I:C)) activates pattern recognition receptors involved in viral sensing and is widely used in alternative animal model of the RNA virus-infected lung injury. In this study, a intratracheal instillation of poly(I:C) with or without IL-6 neutralizing antibody model combined with metabonomics, transcriptomics and so on to explore the underlying molecular mechanisms of IL-6-exacerbated lung injury...

No abstract text is available yet for this article.

No abstract text is available yet for this article.

No abstract text is available yet for this article.