Production of superoxide radicals is a central property of professional phagocytes used to combat invading microorganisms. Even though the number of macrophages and neutrophils is often increased in the lungs of patients with chronic lung diseases, these patients frequently suffer from bacterially induced exacerbations. To understand the underlying mechanisms, we investigated the production of superoxide radicals by bronchoalveolar lavage (BAL) cells in a rat NO(2) exposure model (10 ppm NO(2) for 1, 3, or 20 days). We showed that cells from NO(2)-exposed animals display a significantly impaired superoxide radical release after zymosan stimulation. The use of specific inhibitors (antimycin or diphenyleneiodonium [DPI]) revealed that the major enzyme systems, NADPH oxidase and complex III of the respiratory chain, are affected. In addition, we investigated gene expression and enzyme activities of antioxidant enzymes. mRNA expression was significantly enhanced for glutathione peroxidase (GPx)-3 and CuZn-superoxide dismutase (SOD) in BAL cells from animals exposed 3 and 20 days, and GPx and SOD enzyme activities were increased in BAL cells from rats exposed 20 days. In conclusion, concomitant occurrence of reduced production and increased scavenging of superoxide radicals resulted in the drastically impaired release of these radicals from BAL cells of NO(2)-exposed rats.
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http://dx.doi.org/10.1016/j.freeradbiomed.2004.06.028 | DOI Listing |
Int Immunopharmacol
January 2025
Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai 200032, China; Department of Pulmonary Medicine, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, Fujian 361015, China; Shanghai Key Laboratory of Lung Inflammation and Injury, Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Shanghai Respiratory Research Institute, Shanghai 200032, China.
Acute respiratory distress syndrome (ARDS) is featured with acute lung inflammatory injury. Our prospective study found that higher levels of peroxiredoxin 6(PRDX6) were detected in bronchoalveolar lavage (BAL) fluid from ARDS patients. Elevated PRDX6 was also correlated with monocytic activation and poor prognosis in ARDS patients.
View Article and Find Full Text PDFRespir Res
January 2025
Department of Public Health and Clinical Medicine, Section of Medicine, Umeå University, 901 87, Umeå, Sweden.
Background: In COPD, the balance between matrix metalloproteinases (MMPs) and their natural inhibitors [tissue inhibitors of metalloproteinases (TIMPs)] is shifted towards excessive degradation, reflected in bronchoalveolar lavage (BAL) as increased MMP concentrations. Because of their critical role in lung homeostasis, MMP activity is tightly regulated, but to what extent this regulation occurs through epigenetic mechanisms remains unknown.
Methods: To explore the interplay between MMPs, TIMPs, and DNA methylation (DNAm) we (1) analysed MMP-9, -12, and TIMP-1 concentrations in BAL fluid, and profiled DNAm in BAL cells from 18 COPD and 30 control subjects, (2) estimated protein-COPD relationships using multivariable regression, (3) identified protein quantitative trait methylation loci (pQTMs) with COPD as a potential modifier in a separate interaction model, and (4) integrated significant interactions with a previous COPD GWAS meta-analysis.
J Allergy Clin Immunol
January 2025
Division of Allergy, Pulmonary and Critical Care Medicine, University of Wisconsin-Madison, Madison, Wis. Electronic address:
Background: Airway inflammation has a critical role in asthma pathogenesis and pathophysiology. Yet, the molecular pathways contributing to airway inflammation are not fully known, particularly Type-2 (T2) inflammation characterized by both eosinophilia and higher FeNO levels.
Objective: To identify genes whose level of expression in epithelial brushing samples were associated with both bronchoalveolar lavage (BAL) eosinophilia and generation of FeNO.
Nat Immunol
January 2025
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Hematopoietic stem cells must mitigate myriad stressors throughout their lifetime to ensure normal blood cell generation. Here, we uncover unfolded protein response stress sensor inositol-requiring enzyme-1α (IRE1α) signaling in hematopoietic stem and progenitor cells (HSPCs) as a safeguard against myeloid leukemogenesis. Activated in part by an NADPH oxidase-2 mechanism, IRE1α-induced X-box binding protein-1 (XBP1) mediated repression of pro-leukemogenic programs exemplified by the Wnt-β-catenin pathway.
View Article and Find Full Text PDFViruses
November 2024
C.U.R.E. (University Center for Liver Disease Research and Treatment), Liver Unit, Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy.
SARS-CoV-2 infection induces a humoral immune response, producing virus-specific antibodies such as IgM, IgG, and IgA. IgA antibodies are present at mucosal sites, protecting against respiratory and other mucosal infections, including SARS-CoV-2, by neutralizing viruses or impeding attachment to epithelial cells. Since SARS-CoV-2 spreads through the nasopharynx, the specific IgAs of SARS-CoV-2 are produced quickly after infection, effectively contributing to virus neutralization.
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