American journal of physiology. Lung cellular and molecular physiology最新文献

{"title":"β-Ionone facilitates ex vivo airway smooth muscle relaxation via extraocular opsin-3 light receptor activation.","authors":"Styvalizh Uribe, Eyar Shany, Yi Zhang, Amy D Wu, William Dan, Jose F Perez-Zoghbi, Charles W Emala, Peter D Yim","doi":"10.1152/ajplung.00227.2024","DOIUrl":"10.1152/ajplung.00227.2024","url":null,"abstract":"<p><p>Recent studies have linked deficiencies in β-carotene ingestion and its metabolites with an increased risk and severity of asthma exacerbations. We demonstrate that β-ionone, a β-carotene metabolite, dose-dependently relaxes upper and lower airways in vitro using wire myography of tracheal rings and phase-contrast microscopy of precision-cut lung slices (PCLSs). We demonstrate that β-ionone-induced relaxation is mediated through extraocular opsin-3 (OPN3) receptor activation via pharmacological competitive inhibition with chromophore 9-<i>cis</i> retinal and through the decreased relaxation demonstrated in Opn3-null PCLSs. We implicate a mechanistic pathway suggestive of G_αs activation that is in agreement with our previous findings. Finally, we confirmed OPN3 expression in airway smooth muscle cells by immunofluorescence and mRNA expression. Our findings implicate β-ionone as a potential therapeutic agent for conditions characterized by bronchoconstriction, such as asthma and COPD. Moreover, this study underscores the significance of dietary intake, particularly of β-carotene-rich foods, in maintaining respiratory health.<b>NEW & NOTEWORTHY</b> This research investigates β-ionone's potential as a therapeutic agent for bronchoconstriction. It sheds light on the mechanism of action of β-ionone's activation of extraocular opsin-3 receptors, offering insights into dietary influences on respiratory health. Notably, β-ionone induces dose-dependent relaxation in both upper and lower airways, with attenuated relaxation in Opn3-knockout models confirming receptor selectivity. This study presents a novel approach to addressing respiratory ailments and underscores the significance of dietary components in managing airway pathology.</p>","PeriodicalId":7593,"journal":{"name":"American journal of physiology. Lung cellular and molecular physiology","volume":" ","pages":"L526-L537"},"PeriodicalIF":3.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143405144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TRAPping the effects of tobacco smoking: the regulation and function of <i>Acp5</i> expression in lung macrophages.","authors":"Suzanne H Willems, Shilei Qian, Pernilla Lång, Bjarne E Overtoom, Sina Alimostafazadeh, Rocío Fuentes-Mateos, Gwenda F Vasse, T Anienke van der Veen, Jelmer Vlasma, Marina H de Jager, Victor Guryev, Gyorgy Fejer, Göran Andersson, Barbro N Melgert","doi":"10.1152/ajplung.00157.2024","DOIUrl":"10.1152/ajplung.00157.2024","url":null,"abstract":"<p><p>Tartrate-resistant acid phosphatase [TRAP, gene acid phosphatase 5 (<i>Acp5;</i> gene name for TRAP)] is highly expressed in alveolar macrophages with proposed roles in lung inflammation and lung fibrosis development. We previously showed that its expression and activity are higher in lung macrophages of smokers and patients with chronic obstructive pulmonary disease (COPD), suggesting involvement in smoke-induced lung damage. In this study, we explored the function of TRAP and regulation of its different mRNA transcripts (<i>Acp5 201-206</i>) in lung tissue exposed to cigarette smoke to elucidate its function in alveolar macrophages. In mice exposed to cigarette smoke or air for 4-6 wk, higher <i>Acp5</i> mRNA expression in lung tissue after smoking was mainly driven by transcript <i>Acp5-202</i>, which originates from macrophages. The expression of <i>Acp5-202</i> correlated with transcription factors previously found to drive proliferation of macrophages. Treating fetal liver progenitor-derived alveolar-like macrophages [Max Planck Institute (MPI; macrophages derived from fetal liver progenitors) macrophages] with cigarette smoke extract resulted in more proliferation compared with nontreated cells. In contrast, <i>Acp5</i>-deficient MPI macrophages and MPI macrophages treated with a TRAP inhibitor proliferated significantly less than control macrophages. Mechanistically, this lack of proliferation after TRAP inhibition was associated with higher presence of phosphorylated Beta-catenin (β-catenin; a signaling protein) compared with nontreated controls. Phosphorylation of β-catenin is known to mark it for ubiquitination and degradation by the proteasome, preventing its activity in promoting cell proliferation. In conclusion, our findings provide strong evidence for TRAP stimulating alveolar macrophage proliferation by dephosphorylating β-catenin. By driving proliferation, TRAP likely helps sustain alveolar macrophage populations during smoke exposure, either compensating for their loss due to smoking or increasing their numbers to better manage smoke-induced damage.<b>NEW & NOTEWORTHY</b> This study has uncovered that the enzyme tartrate-resistant acid phosphatase (TRAP) is crucial for alveolar macrophage proliferation through a β-catenin-dependent pathway. Importantly, TRAP influences this important ability of alveolar macrophages through the <i>Acp5</i>-202 mRNA transcript. The increase in TRAP expression following smoke exposure suggests that it plays a key role in promoting cell renewal, potentially helping to mitigate smoke-induced lung damage.</p>","PeriodicalId":7593,"journal":{"name":"American journal of physiology. Lung cellular and molecular physiology","volume":" ","pages":"L497-L511"},"PeriodicalIF":3.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characteristics, triggers, treatments, and experimental models of neonatal acute respiratory distress syndrome.","authors":"Atefeh Mohammadi, Daniele De Luca, Estelle B Gauda","doi":"10.1152/ajplung.00312.2024","DOIUrl":"10.1152/ajplung.00312.2024","url":null,"abstract":"<p><p>Neonatal acute respiratory distress syndrome (NARDS) is a severe and potentially life-threatening form of lung injury recently defined by the International Neonatal ARDS Consensus. It is marked by extensive lung inflammation and damage to the alveolar epithelium and vascular endothelium. NARDS can be triggered by direct inflammatory exposures, such as pneumonia and aspiration, and indirect exposures, including sepsis, necrotizing enterocolitis, and chorioamnionitis. This review provides clinicians and researchers with the latest insights on NARDS. We adopt a cross-disciplinary approach to discuss the diagnostic criteria, pathobiology, triggers, epidemiology, and treatments of NARDS. In addition, we summarize existing clinical studies and advanced preclinical models that help address current knowledge gaps. Future research should focus on standardizing the Montreux consensus definition of NARDS in preclinical and clinical studies, identifying biomarkers, developing prediction models, and exploring novel therapies for affected infants.</p>","PeriodicalId":7593,"journal":{"name":"American journal of physiology. Lung cellular and molecular physiology","volume":" ","pages":"L512-L525"},"PeriodicalIF":3.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic strategies to reverse cigarette smoke-induced ion channel and mucociliary dysfunction in COPD airway epithelial cells.","authors":"Neerupma Silswal, Nathalie Baumlin, Steven Haworth, Robert N Montgomery, Makoto Yoshida, John S Dennis, Sireesha Yerrathota, Michael D Kim, Matthias Salathe","doi":"10.1152/ajplung.00258.2024","DOIUrl":"https://doi.org/10.1152/ajplung.00258.2024","url":null,"abstract":"<p><p>Cigarette smoke (CS) is a leading cause of chronic obstructive pulmonary disease (COPD). Here, we investigated whether the ion channel amplifier nesolicaftor rescues CS-induced mucociliary and ion channel dysfunction. Since CS increases expression of transforming growth factor-beta1 (TGF-β1), human bronchial epithelial cells (HBEC) from healthy donors were used for TGF-β1 and COPD donors (COPD-HBEC) for CS exposure experiments. CS and TGF-β1 induce mucociliary dysfunction by increasing MUC5AC and decreasing ion channel conductance important for mucus hydration. These include cystic fibrosis transmembrane conductance regulator (CFTR) and apical large-conductance, Ca²⁺-activated K⁺ (BK) channels. Nesolicaftor rescued CFTR and BK channel dysfunction, restored ciliary beat frequency (CBF), and decreased mucus viscosity and MUC5AC expression in CS-exposed COPD-HBEC. Nesolicaftor further reversed reductions in ASL volumes, CBF, and CFTR and BK conductance, and blocked the increase in extracellular signal-regulated kinase (ERK) signaling in TGF-β1-exposed normal HBEC. Mechanistically, nesolicaftor increased, as expected, binding of PCBP1 to <i>CFTR</i> mRNA, but surprisingly also to <i>LRRC26</i> mRNA, which encodes the gamma subunit required for BK function. Similar to nesolicaftor, the angiotensin receptor blocker (ARB) losartan rescued TGF-β1-mediated decreases in PCBP1 binding to <i>LRRC26</i> mRNA. In addition, the ARB telmisartan restored PCBP1 binding to <i>CFTR</i> and <i>LRRC26</i> mRNAs to rescue CFTR and BK function in CS-exposed COPD-HBEC. Thus, nesolicaftor and ARBs act on the same target and were therefore neither additive nor synergistic in their actions. These data demonstrate that nesolicaftor and ARBs may provide benefits in COPD by improving ion channel function important for mucus hydration.</p>","PeriodicalId":7593,"journal":{"name":"American journal of physiology. Lung cellular and molecular physiology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143646950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Impact of Electronic Cigarettes on Airway Epithelial Barrier Integrity in Preclinical Mouse Model.","authors":"Amelia L Beaumont, Andjela Raduka, Nannan Gao, Claire E Lee, Robert L Chatburn, Fariba Rezaee","doi":"10.1152/ajplung.00408.2024","DOIUrl":"https://doi.org/10.1152/ajplung.00408.2024","url":null,"abstract":"<p><p>The increasing use of electronic cigarettes (e-cigs) among adolescents poses significant public health risks. This study investigates the impact of e-cigs on the airway epithelial barrier, focusing on apical junctional complexes (AJCs), including tight junctions (TJs) and adherens junctions (AJs). We hypothesized that e-cigs disrupt AJCs in a mouse model, leading to increased airway barrier permeability. C57BL/6 mice were exposed to 36 mg/mL e-cig aerosols (3 puffs per minute) for one hour daily over four days. Bronchoalveolar lavage (BAL) fluid analysis, lung inflammation assessment, immunohistochemistry (IHC) staining, Western blotting (WB), and permeability assays were performed to evaluate the structure and function of the airway barrier. E-cig-exposed mice showed weight loss and elevated serum cotinine levels. BAL fluid analysis revealed elevated white blood cells. Histological analysis confirmed lung inflammation, while IHC and WB showed significant AJC disruption. Notably, claudin-2 levels were elevated in e-cig-exposed mice compared to controls. Claudin-2, known for its role in promoting permeability in \"leaky\" epithelia, increased alongside decreases in other TJ components, signifying structural barrier impairment. After e-cig exposure, instilling FITC-dextran into the airway increased serum FITC-dextran levels, indicating enhanced barrier permeability. E-cig aerosol exposure disrupts airway epithelial barrier structure and function, primarily through the disassembly of TJs and AJs. These findings suggest potential pathways for further clinical investigation into the health risks of e-cig use.</p>","PeriodicalId":7593,"journal":{"name":"American journal of physiology. Lung cellular and molecular physiology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sodium nitrite prevents impaired postnatal alveolar development.","authors":"Kathrine L Daniel, Chantal Gaudet, Ali Hamraghani, Nadya Ben Fadel, Behzad Yeganeh, Robert P Jankov","doi":"10.1152/ajplung.00324.2024","DOIUrl":"https://doi.org/10.1152/ajplung.00324.2024","url":null,"abstract":"<p><p>Deficient nitric oxide (NO) signaling plays a critical role in the pathogenesis of bronchopulmonary dysplasia (BPD); however, clinical trials of inhaled NO (iNO) as preventive therapy for BPD have shown little to no benefit. A biochemical obstacle to effective NO-based therapy relates to the high reactivity of NO, potentially leading to harmful oxidation and nitration. Hypothesizing that nitrite-based therapy has less potential to produce adverse reactions, we compared the preventive effects of sodium nitrite (NaNO₂) and iNO on lung morphology, NO content and signaling, S-nitrosothiols (SNOs) and tyrosine nitration in a novel rat model of experimental BPD. From postnatal days (PND) 1-21, rat pups were exposed to Normoxia or to Hyperoxia-Intermittent Hypoxia ([H-IH]; PND 1-7 85% O₂, PND 7-14 60% O₂ and PND 14-21 normoxia with intermittent exposure to 10% O₂ for 10 min every 4 h) while receiving daily s.c. NaNO₂ (20 mg/kg) or continuous iNO (10 ppm). Controls were treated with vehicle or were not exposed to iNO. Exposure to H-IH caused alveolar and pulmonary vascular hypoplasia, pulmonary hypertension (PH), decreased lung NO content and signaling and increased tyrosine nitration. NaNO₂ prevented abnormal lung morphology and PH, normalized NO content and signaling and prevented nitration. iNO prevented PH, but had minimal effects on abnormal distal airspace morphology, and caused nitration and alveolar hypoplasia in control (normoxia-exposed) animals. Treatment with NaNO₂ increased S-nitrosylation of nine lung proteins; none were increased by iNO. These observations provide a biological rationale for superior efficacy of NaNO₂ in preventing experimental BPD.</p>","PeriodicalId":7593,"journal":{"name":"American journal of physiology. Lung cellular and molecular physiology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Parenchymal and inflammatory responses to ozone exposure in the aging healthy and surfactant protein C mutant lung.","authors":"Jenna R Cheminant, Cassandra E Deering-Rice, Christopher B Massa, Ujjwal Adhikari, Jessica Noll, Christopher A Reilly, Alessandro Venosa","doi":"10.1152/ajplung.00261.2024","DOIUrl":"10.1152/ajplung.00261.2024","url":null,"abstract":"<p><p>Ozone (O₃) is a ubiquitous pollutant known to produce acute, transient inflammation through oxidative injury and inflammation. These effects are exacerbated in susceptible populations, such as the elderly and those exhibiting genetic mutations in central nodes of pulmonary function. To comprehend the impact of these predisposing factors, the present study examines structural, mechanical, and immunological responses to single acute O₃ exposure (0.8 ppm, 3 h) in young (8-14-wk old), middle-aged (44-52-wk old), and old (>80-wk old) mice. Furthermore, this work compares the impact of a clinically relevant mutation in the gene encoding for the alveolar epithelial type 2 specific surfactant protein C. Aging was associated with reduced lung resistance and increases in respiratory elastic properties, the latter of which was exacerbated in SP-C mutant mice. Ozone exposure produced focal injury localized at the terminal bronchiole-to-alveolar junctions and enlarged alveoli in aged SP-C mutant lungs. Flow cytometric analysis revealed increases in mononuclear myeloid abundance in aged SP-C mutant lungs, paired with a contraction in CD8⁺ expressing cells. Expansion of tertiary lymphoid tissues was also noted in aged groups, more evident in the mutant mice. Spatial transcriptomics of CD68⁺ macrophages and CD45^- nonimmune parenchymal cells highlighted age-dependent shifts in inflammatory and extracellular matrix organization signaling, and enrichment in senescence and chromatin remodeling pathways. These results illustrate the structural and immunological impact of O₃ in the aging wild-type and mutant lung and emphasize the significance of modeling environmental exposure in at-risk populations.<b>NEW & NOTEWORTHY</b> Environmental stress and genetic mutations in key functional nodes are linked to the pathogenesis and exacerbation of respiratory pathologies. These responses are exacerbated by aging, though the impact of these factors in combination is not clearly defined. Using a surfactant protein-C mutant line, our studies describe structural changes and phenotypic responses triggered by acute ozone exposure in the young/middle-aged/old lung. Spatial transcriptomics also found regionally distinct and enhanced activation in the aged lung.</p>","PeriodicalId":7593,"journal":{"name":"American journal of physiology. Lung cellular and molecular physiology","volume":" ","pages":"L334-L349"},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineered hydrogel biomaterials facilitate lung progenitor cell differentiation from induced pluripotent stem cells.","authors":"Alicia E Tanneberger, Rachel Blomberg, Ganna Bilousova, Amy L Ryan, Chelsea M Magin","doi":"10.1152/ajplung.00419.2024","DOIUrl":"10.1152/ajplung.00419.2024","url":null,"abstract":"<p><p>Lung progenitor (LP) cells identified by the expression of transcription factor NK2 homeobox 1 (NKX2.1) are essential for the development of all lung epithelial cell types and hold tremendous potential for pulmonary research and translational regenerative medicine applications. Here, we present engineered hydrogels as a promising alternative to the naturally derived materials that are often used to differentiate human-induced pluripotent stem cells (iPSCs) into LP cells. Poly(ethylene glycol) norbornene (PEGNB) hydrogels with defined composition were used to systematically investigate the role of microenvironmental stiffness, cell origin, and splitting during the differentiation process. Results demonstrated that each factor impacted LP differentiation efficiency and that the soft hydrogels replicating healthy lung stiffness [elastic modulus (<i>E</i>) = 4.00 ± 0.25 kPa] produced the highest proportion of LP cells based on flow cytometric analysis results (54%) relative to the stiff hydrogels (48%) and Matrigel controls (32%) at the end of the nonsplit differentiation protocol. Collectively, these results showed that engineered hydrogels provide a well-defined microenvironment for iPSC-to-LP differentiation and perform as effectively as the current gold standard Matrigel-coated tissue culture plastic. Adopting engineered biomaterials in cell culture protocols may enable greater control over differentiation parameters and has the potential to enhance the clinical translation of iPSC-derived LP cells.<b>NEW & NOTEWORTHY</b> Standard iPSC differentiation protocols rely on Matrigel, a basement membrane extract from mouse sarcoma cells that is poorly defined and exhibits significant batch-to-batch variation. Due to these limitations, Matrigel-derived products have never been approved by the Food and Drug Administration. This study introduces a novel method for differentiating iPSCs into lung progenitor cells using well-defined hydrogel substrates. These biomaterials not only enhance differentiation efficiency but also streamline the regulatory pathway, facilitating their potential therapeutic application.</p>","PeriodicalId":7593,"journal":{"name":"American journal of physiology. Lung cellular and molecular physiology","volume":" ","pages":"L379-L388"},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fibrotic and emphysematous murine lung mechanics under negative-pressure ventilation.","authors":"K A M Quiros, T M Nelson, A Ulu, E C Dominguez, T M Nordgren, M Eskandari","doi":"10.1152/ajplung.00087.2024","DOIUrl":"10.1152/ajplung.00087.2024","url":null,"abstract":"<p><p>Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide, and the progressive nature heightens the calamity of the disease. In existing COPD studies, lung mechanics are often reported under positive-pressure ventilation (PPV) and extrapolations made from these studies pose restrictions as recent works have divulged disparate elastic and energetic results between PPV and more physiological negative-pressure ventilation (NPV) counterparts. This nonequivalence of PPV and NPV must be investigated under diseased states to augment our understanding of disease mechanics. To assess the comparability of diseased pulmonary mechanics in PPV and NPV, we pose a novel study to parse out the currently entangled contributions of ventilation mode and diseased state by analyzing murine PV curves from porcine pancreatic elastase (PPE) and hog dust extract (HDE) induced COPD models under positive and negative pressures. We find that, for PPE-exposed, under NPV, volume, compliance (<i>C, C_start</i>, and <i>C_def</i>), and hysteresis are increased in diseased states and that under PPV, only compliance (<i>C</i> and <i>C_start</i>) is increased. For HDE-exposed, under NPV, volume, compliance (<i>C, C_inf</i>, <i>C_def</i>, and <i>K</i>), and hysteresis are decreased, whereas, under PPV, only volume and static compliance decreased. All significant mechanical variations due to disease were observed solely at higher pressures (40 cmH₂O) under both PPV and NPV. Our nuanced conclusions indicate the detection capabilities of multiple mechanics-based biomarkers are sensitive to the ventilation mode, where NPV exhibits more altered mechanics metrics in PPE-exposed and HDE-exposed groups compared with PPV counterparts, suggesting the resolution of biomarkers when applied under NPV research considerations may offer greater versatility.<b>NEW & NOTEWORTHY</b> We evaluate whether ubiquitous pressure-volume (PV) curve biomarkers depend on the ventilation mode under which they were collected (i.e., positive- or negative-pressure ventilation). This is a significant investigation considering recent works have revealed PV curves are distinct and noninterchangeable under the two ventilation modes. Multiple biomarkers noted under negative-pressure ventilation are lacking from positive-pressure counterparts, albeit for small-scale species considerations. Future investigations should confirm the applicability of these findings for large-scale specimens for clinical considerations.</p>","PeriodicalId":7593,"journal":{"name":"American journal of physiology. Lung cellular and molecular physiology","volume":" ","pages":"L443-L455"},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Secondhand vape exposure regulation of CFTR and immune function in cystic fibrosis.","authors":"Benjamin L Wisniewski, Mahesh Shrestha, Dinesh Bojja, Chandra L Shrestha, Chris S Lee, Hazel Ozuna, Rachael E Rayner, Shasha Bai, Estelle Cormet-Boyaka, Susan D Reynolds, Benjamin T Kopp","doi":"10.1152/ajplung.00328.2024","DOIUrl":"10.1152/ajplung.00328.2024","url":null,"abstract":"<p><p>Secondhand smoke exposure (SHSe) is a public health threat for people with cystic fibrosis (CF) and other lung diseases. Primary smoking reduces CF transmembrane conductance regulator (CFTR) channel function, the causative defect in CF. We reported that SHSe worsens respiratory and nutritional outcomes in CF by disrupting immune responses and metabolic signaling. Recently, electronic cigarette (e-cigs) usage by caregivers and peers has increased rapidly, causing new secondhand e-cig vape exposures. Primary vaping is associated with immunologic deficits in healthy people, but it is unknown whether e-cigs similarly impacts CF immune function or how it differs from SHSe. Human CF and non-CF blood monocyte-derived macrophages (MDMs) and bronchial epithelial cells (HBECs) were exposed to flavored and unflavored e-cigs. The effect of e-cigs on CFTR expression and function, bacterial killing, cytokine signaling, lipid mediators, and metabolism was measured during treatment with CFTR modulators. E-cigs decreased CFTR expression and function in CF and non-CF MDMs and negated CFTR functional restoration by elexacaftor/tezacaftor/ivacaftor (ETI). E-cigs also negated the restoration of anti-inflammatory PGD₂ expression in CF MDMs treated with ETI compared with controls. Flavored but not unflavored e-cigs increased proinflammatory cytokine expression in CF MDMs and e-cigs promoted glycolytic metabolism. E-cigs did not impact bacterial killing. Overall, HBECs were less impacted by e-cigs compared with MDMs. E-cigs reduced macrophage CFTR expression and hindered functional CFTR restoration by CFTR modulators, promoting a glycolytic, proinflammatory state. E-cigs are an emerging public health threat that may limit the efficacy of CFTR modulators in people with CF.<b>NEW & NOTEWORTHY</b> New research reveals that e-cigarettes pose a serious health risk for individuals with cystic fibrosis (CF). Exposure to electronic cigarette (e-cig) vapors decreases CF transmembrane conductance regulator (CFTR) function and undermines the effectiveness of CFTR modulators, potentially worsening inflammation and metabolic responses. This highlights an urgent need for awareness around e-cig use, especially among caregivers and peers of those with CF. E-cigarettes may further complicate the management of this chronic lung disease.</p>","PeriodicalId":7593,"journal":{"name":"American journal of physiology. Lung cellular and molecular physiology","volume":" ","pages":"L324-L333"},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}