Cell-free hemoglobin triggers macrophage cytokine production via TLR4 and MyD88
Am J Physiol Lung Cell Mol Physiol. 2023 Nov 22. doi: 10.1152/ajplung.00123.2023. Online ahead of print.ABSTRACTCell-free hemoglobin (CFH) is elevated in the airspace of patients with acute respiratory distress syndrome (ARDS) and is sufficient to cause acute lung injury in a murine model. However, the pathways through which CFH causes lung injury are not well understood. Toll-like receptor 4 (TLR4) is a mediator of inflammation after detection of damage- and pathogen-associated molecular patterns. We hypothesized that TLR4 signaling mediates the pro-inflammatory effects of CFH in the airspace. After intra-tracheal CFH, BA...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - November 22, 2023 Category: Cytology Authors: Kaitlyn R Schaaf Stuart R Landstreet Sangami Pugazenthi Emily Y Qian Nathan D Putz Tatiana Siderova Allison M Owen Julia K Bohannon Lorraine B Ware Julie A Bastarache Ciara M Shaver Source Type: research

Functional Role of Glial Derived Neurotrophic Factor in a Mixed Allergen Murine Model of Asthma
In this study, we tested the hypothesis that airway GDNF contributes to airway hyperreactivity (AHR) and remodeling using a mixed allergen mouse model. Adult C57BL/6J mice were intranasally exposed to mixed allergens (ovalbumin, Aspergillus, Alternaria, house dust mite) over 4 weeks with concurrent exposure to recombinant GDNF, or extracellular GDNF chelator GFRα1-Fc. Airway resistance and compliance to methacholine were assessed using FlexiVent. Lung expression of GDNF, GFRα1, RET, collagen, and fibronectin was examined by RT-PCR and histology staining. Allergen exposure increased GDNF expression in bronchial airways in...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - November 21, 2023 Category: Cytology Authors: Li Y Drake Sarah A Wicher Benjamin B Roos Latifa Khalfaoui Lisa Nesbitt Yun Hua Fang Christina M Pabelick Y S Prakash Source Type: research

Exogenous hydrogen sulfide attenuates hyperoxia effects on neonatal mouse airways
Am J Physiol Lung Cell Mol Physiol. 2023 Nov 21. doi: 10.1152/ajplung.00196.2023. Online ahead of print.ABSTRACTSupplemental O2 remains a necessary intervention for many premature infants (<34 weeks gestation). Even moderate hyperoxia (<60% O2) poses a risk for subsequent airway disease, thereby predisposing premature infants to pediatric asthma involving chronic inflammation, airway hyperresponsiveness (AHR), airway remodeling, and airflow obstruction. Moderate hyperoxia promotes AHR via effects on airway smooth muscle (ASM), a cell type that also contribute to impaired bronchodilation and remodeling (proliferation,...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - November 21, 2023 Category: Cytology Authors: Colleen M Bartman Marta Schiliro Lisa Nesbitt Kenge K Lee Y S Prakash Christina M Pabelick Source Type: research

Bariatric Surgery Decreases the Capacity of Plasma from Obese Asthmatic Subjects to Augment Airway Epithelial Cell Pro-Inflammatory Cytokine Production
Am J Physiol Lung Cell Mol Physiol. 2023 Nov 21. doi: 10.1152/ajplung.00205.2023. Online ahead of print.ABSTRACTObesity is a risk factor asthma. People with asthma and obesity often have poor control and do not respond as well to therapies such as inhaled corticosteroids and long-acting bronchodilators. Weight loss improves asthma control, with a 5-10% loss in body mass necessary and sufficient to lead to clinically relevant improvements. Preclinical studies have demonstrated the pathogenic contribution of adipocytes from obese mice to the augmented production of pro-inflammatory cytokines from airway epithelial cells, and...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - November 21, 2023 Category: Cytology Authors: Paola E Pe ña-Garcia V Amanda Fastiggi Madeleine M Mank Jennifer L Ather Olivia J Garrow Vikas Anathy Anne E Dixon Matthew E Poynter Source Type: research

Functional Role of Glial Derived Neurotrophic Factor in a Mixed Allergen Murine Model of Asthma
In this study, we tested the hypothesis that airway GDNF contributes to airway hyperreactivity (AHR) and remodeling using a mixed allergen mouse model. Adult C57BL/6J mice were intranasally exposed to mixed allergens (ovalbumin, Aspergillus, Alternaria, house dust mite) over 4 weeks with concurrent exposure to recombinant GDNF, or extracellular GDNF chelator GFRα1-Fc. Airway resistance and compliance to methacholine were assessed using FlexiVent. Lung expression of GDNF, GFRα1, RET, collagen, and fibronectin was examined by RT-PCR and histology staining. Allergen exposure increased GDNF expression in bronchial airways in...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - November 21, 2023 Category: Cytology Authors: Li Y Drake Sarah A Wicher Benjamin B Roos Latifa Khalfaoui Lisa Nesbitt Yun Hua Fang Christina M Pabelick Y S Prakash Source Type: research

Exogenous hydrogen sulfide attenuates hyperoxia effects on neonatal mouse airways
Am J Physiol Lung Cell Mol Physiol. 2023 Nov 21. doi: 10.1152/ajplung.00196.2023. Online ahead of print.ABSTRACTSupplemental O2 remains a necessary intervention for many premature infants (<34 weeks gestation). Even moderate hyperoxia (<60% O2) poses a risk for subsequent airway disease, thereby predisposing premature infants to pediatric asthma involving chronic inflammation, airway hyperresponsiveness (AHR), airway remodeling, and airflow obstruction. Moderate hyperoxia promotes AHR via effects on airway smooth muscle (ASM), a cell type that also contribute to impaired bronchodilation and remodeling (proliferation,...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - November 21, 2023 Category: Cytology Authors: Colleen M Bartman Marta Schiliro Lisa Nesbitt Kenge K Lee Y S Prakash Christina M Pabelick Source Type: research

The alveolar fibroproliferative response in moderate to severe COVID-19-related acute respiratory distress syndrome and one-year follow up
CONCLUSION: In COVID-19-ARDS patients, alveolar FPR during hospitalization was associated with higher mortality but not with the presence of long-term fibrotic lung sequelae within survivors.PMID:37933449 | DOI:10.1152/ajplung.00156.2023 (Source: American Journal of Physiology. Lung Cellular and Molecular Physiology)
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - November 7, 2023 Category: Cytology Authors: Shiqi Zhang Leonoor S Boers Justin de Brabander Laura B van den Heuvel Siebe G Blok Robert F J Kullberg Barbara S Smids-Dierdorp Tamara Dekker Hella L Aberson Lilian J Meijboom Alexander P J Vlaar Leo Heunks Esther J Nossent Tom van der Poll Lieuwe D J Bo Source Type: research

Genetic deficiency of the transcription factor NFAT1 confers protection against fibrogenic responses independent of immune influx
Am J Physiol Lung Cell Mol Physiol. 2023 Nov 7. doi: 10.1152/ajplung.00045.2023. Online ahead of print.ABSTRACTIdiopathic pulmonary fibrosis (IPF) is marked by unremitting matrix deposition and architectural distortion. Multiple pro-fibrotic pathways contribute to the persistent activation of mesenchymal cells (MCs) in fibrosis, highlighting the need to identify and target common signaling pathways. The transcription factor NFAT1 (nuclear factor of activated T cells 1) lies downstream of second messenger calcium signaling and has been recently shown to regulate key pro-fibrotic mediator autotaxin (ATX) in lung MCs. Herein,...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - November 7, 2023 Category: Cytology Authors: Ragini Vittal Natalie M Walker A Patrick McLinden Russell R Braeuer Fang Ke Fatemeh Fattahi Michael P Combs Keizo Misumi Yoshiro Aoki David S Wheeler Carol A Wilke Steven K Huang Bethany B Moore Pengxiu Cao Vibha N Lama Source Type: research

Changes in respiratory mechanics in response to crystalloid infusions in extremely premature infants
Am J Physiol Lung Cell Mol Physiol. 2023 Nov 7. doi: 10.1152/ajplung.00179.2023. Online ahead of print.ABSTRACTExtremely premature infants are at a higher risk of developing respiratory distress syndrome and circulatory impairments in the first few weeks of life. Administration of normal saline bolus is a common practice to manage hypotension in preterm infants. As a crystalloid, a substantial proportion might leak into the interstitium; most consequently the lungs in the preterm cohorts, putatively affecting ventilation. We downloaded and analysed ventilator mechanics data in infants managed by conventional mechanical ven...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - November 7, 2023 Category: Cytology Authors: Arvind Sehgal Bishal Gauli Source Type: research

Nicotine Affects Mitochondrial Structure and Function in Human Airway Smooth Muscle Cells
Am J Physiol Lung Cell Mol Physiol. 2023 Nov 7. doi: 10.1152/ajplung.00158.2023. Online ahead of print.ABSTRACTExposure to cigarette smoke and e-cigarettes, with nicotine as the active constituent, contributes to increased health risks associated with asthma. Nicotine exerts its functional activity via nicotinic acetylcholine receptors (nAChRs) and the alpha7 subtype (α7nAChR) has recently been shown to adversely affect airway dynamics. The mechanisms of α7nAChR action in airways, particularly in the context of airway smooth muscle (ASM), a key cell type in asthma, are still under investigation. Mitochondria have garnere...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - November 7, 2023 Category: Cytology Authors: Niyati A Borkar Michael A Thompson Colleen M Bartman Venkatachalem Sathish Y S Prakash Christina M Pabelick Source Type: research

The alveolar fibroproliferative response in moderate to severe COVID-19-related acute respiratory distress syndrome and one-year follow up
CONCLUSION: In COVID-19-ARDS patients, alveolar FPR during hospitalization was associated with higher mortality but not with the presence of long-term fibrotic lung sequelae within survivors.PMID:37933449 | DOI:10.1152/ajplung.00156.2023 (Source: American Journal of Physiology. Lung Cellular and Molecular Physiology)
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - November 7, 2023 Category: Cytology Authors: Shiqi Zhang Leonoor S Boers Justin de Brabander Laura B van den Heuvel Siebe G Blok Robert F J Kullberg Barbara S Smids-Dierdorp Tamara Dekker Hella L Aberson Lilian J Meijboom Alexander P J Vlaar Leo Heunks Esther J Nossent Tom van der Poll Lieuwe D J Bo Source Type: research

Genetic deficiency of the transcription factor NFAT1 confers protection against fibrogenic responses independent of immune influx
Am J Physiol Lung Cell Mol Physiol. 2023 Nov 7. doi: 10.1152/ajplung.00045.2023. Online ahead of print.ABSTRACTIdiopathic pulmonary fibrosis (IPF) is marked by unremitting matrix deposition and architectural distortion. Multiple pro-fibrotic pathways contribute to the persistent activation of mesenchymal cells (MCs) in fibrosis, highlighting the need to identify and target common signaling pathways. The transcription factor NFAT1 (nuclear factor of activated T cells 1) lies downstream of second messenger calcium signaling and has been recently shown to regulate key pro-fibrotic mediator autotaxin (ATX) in lung MCs. Herein,...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - November 7, 2023 Category: Cytology Authors: Ragini Vittal Natalie M Walker A Patrick McLinden Russell R Braeuer Fang Ke Fatemeh Fattahi Michael P Combs Keizo Misumi Yoshiro Aoki David S Wheeler Carol A Wilke Steven K Huang Bethany B Moore Pengxiu Cao Vibha N Lama Source Type: research

Changes in respiratory mechanics in response to crystalloid infusions in extremely premature infants
Am J Physiol Lung Cell Mol Physiol. 2023 Nov 7. doi: 10.1152/ajplung.00179.2023. Online ahead of print.ABSTRACTExtremely premature infants are at a higher risk of developing respiratory distress syndrome and circulatory impairments in the first few weeks of life. Administration of normal saline bolus is a common practice to manage hypotension in preterm infants. As a crystalloid, a substantial proportion might leak into the interstitium; most consequently the lungs in the preterm cohorts, putatively affecting ventilation. We downloaded and analysed ventilator mechanics data in infants managed by conventional mechanical ven...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - November 7, 2023 Category: Cytology Authors: Arvind Sehgal Bishal Gauli Source Type: research

Nicotine Affects Mitochondrial Structure and Function in Human Airway Smooth Muscle Cells
Am J Physiol Lung Cell Mol Physiol. 2023 Nov 7. doi: 10.1152/ajplung.00158.2023. Online ahead of print.ABSTRACTExposure to cigarette smoke and e-cigarettes, with nicotine as the active constituent, contributes to increased health risks associated with asthma. Nicotine exerts its functional activity via nicotinic acetylcholine receptors (nAChRs) and the alpha7 subtype (α7nAChR) has recently been shown to adversely affect airway dynamics. The mechanisms of α7nAChR action in airways, particularly in the context of airway smooth muscle (ASM), a key cell type in asthma, are still under investigation. Mitochondria have garnere...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - November 7, 2023 Category: Cytology Authors: Niyati A Borkar Michael A Thompson Colleen M Bartman Venkatachalem Sathish Y S Prakash Christina M Pabelick Source Type: research

The alveolar fibroproliferative response in moderate to severe COVID-19-related acute respiratory distress syndrome and one-year follow up
CONCLUSION: In COVID-19-ARDS patients, alveolar FPR during hospitalization was associated with higher mortality but not with the presence of long-term fibrotic lung sequelae within survivors.PMID:37933449 | DOI:10.1152/ajplung.00156.2023 (Source: American Journal of Physiology. Lung Cellular and Molecular Physiology)
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - November 7, 2023 Category: Cytology Authors: Shiqi Zhang Leonoor S Boers Justin de Brabander Laura B van den Heuvel Siebe G Blok Robert F J Kullberg Barbara S Smids-Dierdorp Tamara Dekker Hella L Aberson Lilian J Meijboom Alexander P J Vlaar Leo Heunks Esther J Nossent Tom van der Poll Lieuwe D J Bo Source Type: research