Neutrophil and airway epithelial cell interactions are critical in the inflammatory response to viral infections including respiratory syncytial virus, Sendai virus, and SARS-CoV-2. Airway epithelial cell dysfunction during viral infections is likely mediated by the interaction of virus and recruited neutrophils at the airway epithelial barrier. Neutrophils are key early responders to viral infection. Neutrophil myeloperoxidase catalyzes the conversion of hydrogen peroxide to hypochlorous acid (HOCl). Previous studies have shown HOCl targets host neutrophil and endothelial cell plasmalogen lipids, resulting in the production of the chlorinated lipid, 2-chlorofatty aldehyde (2-ClFALD). We have previously shown that the oxidation product of 2-ClFALD, 2-chlorofatty acid (2-ClFA) is present in bronchoalveolar lavage fluid of Sendai virus-infected mice, which likely results from the attack of the epithelial plasmalogen by neutrophil-derived HOCl. Herein, we demonstrate small airway epithelial cells contain plasmalogens enriched with oleic acid at the sn-2 position unlike endothelial cells which contain arachidonic acid enrichment at the sn-2 position of plasmalogen. We also show neutrophil-derived HOCl targets epithelial cell plasmalogens to produce 2-ClFALD. Further, proteomics and over-representation analysis using the ω-alkyne analog of the 2-ClFALD molecular species, 2-chlorohexadecanal (2-ClHDyA) showed cell adhesion molecule binding and cell-cell junction enriched categories similar to that observed previously in endothelial cells. However, in contrast to endothelial cells, proteins in distinct metabolic pathways were enriched with 2-ClFALD modification, particularly pyruvate metabolism was enriched in epithelial cells and mitochondrial pyruvate respiration was reduced. Collectively, these studies demonstrate, for the first time, a novel plasmalogen molecular species distribution in airway epithelial cells that are targeted by myeloperoxidase-derived hypochlorous acid resulting in electrophilic 2-ClFALD, which potentially modifies epithelial physiology by modifying proteins.
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http://dx.doi.org/10.1016/j.redox.2022.102557 | DOI Listing |
Sci Adv
January 2025
Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA, USA.
Oxygen controls most metazoan metabolism, yet in mammals, tissue O levels vary widely. While extensive research has explored cellular responses to hypoxia, understanding how cells respond to physiologically high O levels remains uncertain. To address this problem, we investigated respiratory epithelia as their contact with air exposes them to some of the highest O levels in the body.
View Article and Find Full Text PDFThere is increased interest in developing non-animal test systems for inhalation exposure safety assessments. However, defined methodologies are absent for predicting local respiratory effects from inhalation exposure to irritants. The current study introduces a concept for applying in vitro and in silico methods for inhalation exposure safety assessment.
View Article and Find Full Text PDFAnn Card Anaesth
January 2025
All India Institute of Medical Sciences, Raipur, Chhattisgarh, India.
Pulmonary alveolar proteinosis (PAP) is a rare pulmonary pathology characterized by the accumulation of surfactant within type II alveolar epithelial cells. Whole lung lavage is the standard treatment for pulmonary alveolar proteinosis involving a large volume of fluid is infused into one lung and subsequently retrieved while the other lung is remains ventilated. Fast-tracking a patient undergoing whole lung lavage requires vigilant monitoring of arterial blood gases, fluid status, and respiratory mechanics.
View Article and Find Full Text PDFEnviron Epigenet
January 2025
Institute of Human Genetics, School of Medicine, Pontificia Universidad Javeriana, Bogotá 110231, Colombia.
Fine particulate matter (PM), an atmospheric pollutant that settles deep in the respiratory tract, is highly harmful to human health. Despite its well-known impact on lung function and its ability to exacerbate asthma, the molecular basis of this effect is not fully understood. This integrated transcriptomic and epigenomic data analysis from publicly available datasets aimed to determine the impact of PM exposure and its association with asthma in human airway epithelial cells.
View Article and Find Full Text PDFJ Microbiol Biotechnol
December 2024
Institute of Agricultural Science and Technology, Kyungpook National University, Daegu 41566, Republic of Korea.
L. (noni) is native to the tropical and semitropical areas and has been commercially available in health food stores and chain grocery stores specializing in natural foods, recently. Noni seeds are discarded as waste products through the industrial production of noni juice even though their bioactivity components might be a potential source of functional foods.
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