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Open Access | 10.1172/jci.insight.181024
1Cardiovascular Research Institute, UCSF, San Francisco, United States of America
2Department of Chemical Engineering, Stanford University, Stanford, United States of America
3Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, UCSF, San Francisco, United States of America
4Division of Pulmonary, Critical Care and Sleep Medicine, University of Kansas School of Medicine, Kansas City, United States of America
5Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, United States of America
6Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, United States of America
7Division of Allergy, Pulmonary, and Critical Care Medicine, University of Wisconsin School of Medicine and Public Health, Madison, United States of America
8Department of Internal Medicine, Section on Pulmonary, Critical Care, Aller, Wake Forest University School of Medicine, Winston-Salem, United States of America
9Department of Environmental and Occupational Health, Asthma and Environmental Lung Health Institute at UPMC, Pittsburgh, United States of America
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1Cardiovascular Research Institute, UCSF, San Francisco, United States of America
2Department of Chemical Engineering, Stanford University, Stanford, United States of America
3Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, UCSF, San Francisco, United States of America
4Division of Pulmonary, Critical Care and Sleep Medicine, University of Kansas School of Medicine, Kansas City, United States of America
5Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, United States of America
6Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, United States of America
7Division of Allergy, Pulmonary, and Critical Care Medicine, University of Wisconsin School of Medicine and Public Health, Madison, United States of America
8Department of Internal Medicine, Section on Pulmonary, Critical Care, Aller, Wake Forest University School of Medicine, Winston-Salem, United States of America
9Department of Environmental and Occupational Health, Asthma and Environmental Lung Health Institute at UPMC, Pittsburgh, United States of America
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1Cardiovascular Research Institute, UCSF, San Francisco, United States of America
2Department of Chemical Engineering, Stanford University, Stanford, United States of America
3Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, UCSF, San Francisco, United States of America
4Division of Pulmonary, Critical Care and Sleep Medicine, University of Kansas School of Medicine, Kansas City, United States of America
5Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, United States of America
6Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, United States of America
7Division of Allergy, Pulmonary, and Critical Care Medicine, University of Wisconsin School of Medicine and Public Health, Madison, United States of America
8Department of Internal Medicine, Section on Pulmonary, Critical Care, Aller, Wake Forest University School of Medicine, Winston-Salem, United States of America
9Department of Environmental and Occupational Health, Asthma and Environmental Lung Health Institute at UPMC, Pittsburgh, United States of America
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1Cardiovascular Research Institute, UCSF, San Francisco, United States of America
2Department of Chemical Engineering, Stanford University, Stanford, United States of America
3Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, UCSF, San Francisco, United States of America
4Division of Pulmonary, Critical Care and Sleep Medicine, University of Kansas School of Medicine, Kansas City, United States of America
5Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, United States of America
6Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, United States of America
7Division of Allergy, Pulmonary, and Critical Care Medicine, University of Wisconsin School of Medicine and Public Health, Madison, United States of America
8Department of Internal Medicine, Section on Pulmonary, Critical Care, Aller, Wake Forest University School of Medicine, Winston-Salem, United States of America
9Department of Environmental and Occupational Health, Asthma and Environmental Lung Health Institute at UPMC, Pittsburgh, United States of America
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1Cardiovascular Research Institute, UCSF, San Francisco, United States of America
2Department of Chemical Engineering, Stanford University, Stanford, United States of America
3Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, UCSF, San Francisco, United States of America
4Division of Pulmonary, Critical Care and Sleep Medicine, University of Kansas School of Medicine, Kansas City, United States of America
5Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, United States of America
6Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, United States of America
7Division of Allergy, Pulmonary, and Critical Care Medicine, University of Wisconsin School of Medicine and Public Health, Madison, United States of America
8Department of Internal Medicine, Section on Pulmonary, Critical Care, Aller, Wake Forest University School of Medicine, Winston-Salem, United States of America
9Department of Environmental and Occupational Health, Asthma and Environmental Lung Health Institute at UPMC, Pittsburgh, United States of America
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1Cardiovascular Research Institute, UCSF, San Francisco, United States of America
2Department of Chemical Engineering, Stanford University, Stanford, United States of America
3Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, UCSF, San Francisco, United States of America
4Division of Pulmonary, Critical Care and Sleep Medicine, University of Kansas School of Medicine, Kansas City, United States of America
5Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, United States of America
6Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, United States of America
7Division of Allergy, Pulmonary, and Critical Care Medicine, University of Wisconsin School of Medicine and Public Health, Madison, United States of America
8Department of Internal Medicine, Section on Pulmonary, Critical Care, Aller, Wake Forest University School of Medicine, Winston-Salem, United States of America
9Department of Environmental and Occupational Health, Asthma and Environmental Lung Health Institute at UPMC, Pittsburgh, United States of America
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1Cardiovascular Research Institute, UCSF, San Francisco, United States of America
2Department of Chemical Engineering, Stanford University, Stanford, United States of America
3Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, UCSF, San Francisco, United States of America
4Division of Pulmonary, Critical Care and Sleep Medicine, University of Kansas School of Medicine, Kansas City, United States of America
5Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, United States of America
6Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, United States of America
7Division of Allergy, Pulmonary, and Critical Care Medicine, University of Wisconsin School of Medicine and Public Health, Madison, United States of America
8Department of Internal Medicine, Section on Pulmonary, Critical Care, Aller, Wake Forest University School of Medicine, Winston-Salem, United States of America
9Department of Environmental and Occupational Health, Asthma and Environmental Lung Health Institute at UPMC, Pittsburgh, United States of America
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1Cardiovascular Research Institute, UCSF, San Francisco, United States of America
2Department of Chemical Engineering, Stanford University, Stanford, United States of America
3Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, UCSF, San Francisco, United States of America
4Division of Pulmonary, Critical Care and Sleep Medicine, University of Kansas School of Medicine, Kansas City, United States of America
5Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, United States of America
6Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, United States of America
7Division of Allergy, Pulmonary, and Critical Care Medicine, University of Wisconsin School of Medicine and Public Health, Madison, United States of America
8Department of Internal Medicine, Section on Pulmonary, Critical Care, Aller, Wake Forest University School of Medicine, Winston-Salem, United States of America
9Department of Environmental and Occupational Health, Asthma and Environmental Lung Health Institute at UPMC, Pittsburgh, United States of America
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1Cardiovascular Research Institute, UCSF, San Francisco, United States of America
2Department of Chemical Engineering, Stanford University, Stanford, United States of America
3Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, UCSF, San Francisco, United States of America
4Division of Pulmonary, Critical Care and Sleep Medicine, University of Kansas School of Medicine, Kansas City, United States of America
5Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, United States of America
6Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, United States of America
7Division of Allergy, Pulmonary, and Critical Care Medicine, University of Wisconsin School of Medicine and Public Health, Madison, United States of America
8Department of Internal Medicine, Section on Pulmonary, Critical Care, Aller, Wake Forest University School of Medicine, Winston-Salem, United States of America
9Department of Environmental and Occupational Health, Asthma and Environmental Lung Health Institute at UPMC, Pittsburgh, United States of America
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1Cardiovascular Research Institute, UCSF, San Francisco, United States of America
2Department of Chemical Engineering, Stanford University, Stanford, United States of America
3Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, UCSF, San Francisco, United States of America
4Division of Pulmonary, Critical Care and Sleep Medicine, University of Kansas School of Medicine, Kansas City, United States of America
5Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, United States of America
6Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, United States of America
7Division of Allergy, Pulmonary, and Critical Care Medicine, University of Wisconsin School of Medicine and Public Health, Madison, United States of America
8Department of Internal Medicine, Section on Pulmonary, Critical Care, Aller, Wake Forest University School of Medicine, Winston-Salem, United States of America
9Department of Environmental and Occupational Health, Asthma and Environmental Lung Health Institute at UPMC, Pittsburgh, United States of America
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1Cardiovascular Research Institute, UCSF, San Francisco, United States of America
2Department of Chemical Engineering, Stanford University, Stanford, United States of America
3Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, UCSF, San Francisco, United States of America
4Division of Pulmonary, Critical Care and Sleep Medicine, University of Kansas School of Medicine, Kansas City, United States of America
5Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, United States of America
6Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, United States of America
7Division of Allergy, Pulmonary, and Critical Care Medicine, University of Wisconsin School of Medicine and Public Health, Madison, United States of America
8Department of Internal Medicine, Section on Pulmonary, Critical Care, Aller, Wake Forest University School of Medicine, Winston-Salem, United States of America
9Department of Environmental and Occupational Health, Asthma and Environmental Lung Health Institute at UPMC, Pittsburgh, United States of America
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1Cardiovascular Research Institute, UCSF, San Francisco, United States of America
2Department of Chemical Engineering, Stanford University, Stanford, United States of America
3Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, UCSF, San Francisco, United States of America
4Division of Pulmonary, Critical Care and Sleep Medicine, University of Kansas School of Medicine, Kansas City, United States of America
5Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, United States of America
6Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, United States of America
7Division of Allergy, Pulmonary, and Critical Care Medicine, University of Wisconsin School of Medicine and Public Health, Madison, United States of America
8Department of Internal Medicine, Section on Pulmonary, Critical Care, Aller, Wake Forest University School of Medicine, Winston-Salem, United States of America
9Department of Environmental and Occupational Health, Asthma and Environmental Lung Health Institute at UPMC, Pittsburgh, United States of America
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1Cardiovascular Research Institute, UCSF, San Francisco, United States of America
2Department of Chemical Engineering, Stanford University, Stanford, United States of America
3Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, UCSF, San Francisco, United States of America
4Division of Pulmonary, Critical Care and Sleep Medicine, University of Kansas School of Medicine, Kansas City, United States of America
5Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, United States of America
6Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, United States of America
7Division of Allergy, Pulmonary, and Critical Care Medicine, University of Wisconsin School of Medicine and Public Health, Madison, United States of America
8Department of Internal Medicine, Section on Pulmonary, Critical Care, Aller, Wake Forest University School of Medicine, Winston-Salem, United States of America
9Department of Environmental and Occupational Health, Asthma and Environmental Lung Health Institute at UPMC, Pittsburgh, United States of America
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1Cardiovascular Research Institute, UCSF, San Francisco, United States of America
2Department of Chemical Engineering, Stanford University, Stanford, United States of America
3Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, UCSF, San Francisco, United States of America
4Division of Pulmonary, Critical Care and Sleep Medicine, University of Kansas School of Medicine, Kansas City, United States of America
5Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, United States of America
6Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, United States of America
7Division of Allergy, Pulmonary, and Critical Care Medicine, University of Wisconsin School of Medicine and Public Health, Madison, United States of America
8Department of Internal Medicine, Section on Pulmonary, Critical Care, Aller, Wake Forest University School of Medicine, Winston-Salem, United States of America
9Department of Environmental and Occupational Health, Asthma and Environmental Lung Health Institute at UPMC, Pittsburgh, United States of America
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1Cardiovascular Research Institute, UCSF, San Francisco, United States of America
2Department of Chemical Engineering, Stanford University, Stanford, United States of America
3Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, UCSF, San Francisco, United States of America
4Division of Pulmonary, Critical Care and Sleep Medicine, University of Kansas School of Medicine, Kansas City, United States of America
5Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, United States of America
6Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, United States of America
7Division of Allergy, Pulmonary, and Critical Care Medicine, University of Wisconsin School of Medicine and Public Health, Madison, United States of America
8Department of Internal Medicine, Section on Pulmonary, Critical Care, Aller, Wake Forest University School of Medicine, Winston-Salem, United States of America
9Department of Environmental and Occupational Health, Asthma and Environmental Lung Health Institute at UPMC, Pittsburgh, United States of America
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1Cardiovascular Research Institute, UCSF, San Francisco, United States of America
2Department of Chemical Engineering, Stanford University, Stanford, United States of America
3Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, UCSF, San Francisco, United States of America
4Division of Pulmonary, Critical Care and Sleep Medicine, University of Kansas School of Medicine, Kansas City, United States of America
5Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, United States of America
6Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, United States of America
7Division of Allergy, Pulmonary, and Critical Care Medicine, University of Wisconsin School of Medicine and Public Health, Madison, United States of America
8Department of Internal Medicine, Section on Pulmonary, Critical Care, Aller, Wake Forest University School of Medicine, Winston-Salem, United States of America
9Department of Environmental and Occupational Health, Asthma and Environmental Lung Health Institute at UPMC, Pittsburgh, United States of America
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Published June 18, 2024 - More info
Mucus plugs occlude airways to obstruct airflow in asthma. Studies in patients and in mouse models show that mucus plugs occur in the context of type 2 inflammation, and studies in human airway epithelial cells (HAECs) show that interleukin 13 (IL-13) activated cells generate pathologic mucus independently of immune cells. To determine how HAECs autonomously generate pathologic mucus, we used a magnetic microwire rheometer to characterize the viscoelastic properties of mucus secreted under varying conditions. We found that normal HAEC mucus exhibits viscoelastic liquid behavior and that mucus secreted by IL-13 activated HAECs exhibits solid-like behavior caused by mucin cross-linking. In addition, IL-13 activated HAECs show increased peroxidase activity in apical secretions, and an overlaid thiolated polymer (thiomer) solution shows an increase in solid behavior that is prevented by peroxidase inhibition. Furthermore, gene expression for thyroid peroxidase (TPO), but not lactoperoxidase (LPO), is increased in IL-13 activated HAECs and both TPO and LPO catalyze the formation of oxidant acids that cross-link thiomer solutions. Finally, gene expression for TPO in airway epithelial brushings is increased in asthma patients with high airway mucus plug scores. Together, our results show that IL-13 activated HAECs autonomously generate pathologic mucus via peroxidase-mediated cross-linking of mucin polymers.