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Airway acidification initiates host defense abnormalities in cystic fibrosis mice.

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Title: Airway acidification initiates host defense abnormalities in cystic fibrosis mice.
Authors: Shah, Viral S., Meyerholz, David K., Xiao Xiao Tang, Reznikov, Leah, Alaiwa, Mahmoud Abou, Ernst, Sarah E., Karp, Philip H., Wohlford-Lenane, Christine L., Heilmann, Kristopher P., Leidinger, Mariah R., Allen, Patrick D., Zabner, Joseph, McCray Jr, Paul B., Ostedgaard, Lynda S., Stoltz, David A., Randak, Christoph O., Welsh, Michael J.
Source: Science (pre-March 2025). 1/29/2016, Vol. 351 Issue 6272, p503-507. 5p.
Subjects: Acidification, Cystic fibrosis, Laboratory mice, Bicarbonate ions, Genetic mutation
Abstract: Cystic fibrosis (CF) is caused by mutations in the gene that encodes the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel. In humans and pigs, the loss of CFTR impairs respiratory host defenses, causing airway infection. But CF mice are spared. We found that in all three species, CFTR secreted bicarbonate into airway surface liquid. In humans and pigs lacking CFTR, unchecked H+ secretion by the nongastric H+/K+ adenosine triphosphatase (ATP12A) acidified airway surface liquid, which impaired airway host defenses. In contrast, mouse airways expressed little ATP12A and secreted minimal H+; consequently, airway surface liquid in CF and non-CF mice had similar pH. Inhibiting ATP12A reversed host defense abnormalities in human and pig airways. Conversely, expressing ATP12A in CF mouse airways acidified airway surface liquid, impaired defenses, and increased airway bacteria. These findings help explain why CF mice are protected from infection and nominate ATP12A as a potential therapeutic target for CF. [ABSTRACT FROM AUTHOR]
Copyright of Science (pre-March 2025) is the property of American Association for the Advancement of Science and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
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  Data: Airway acidification initiates host defense abnormalities in cystic fibrosis mice.
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  Data: <searchLink fieldCode="AR" term="%22Shah%2C+Viral+S%2E%22">Shah, Viral S.</searchLink><br /><searchLink fieldCode="AR" term="%22Meyerholz%2C+David+K%2E%22">Meyerholz, David K.</searchLink><br /><searchLink fieldCode="AR" term="%22Xiao+Xiao+Tang%22">Xiao Xiao Tang</searchLink><br /><searchLink fieldCode="AR" term="%22Reznikov%2C+Leah%22">Reznikov, Leah</searchLink><br /><searchLink fieldCode="AR" term="%22Alaiwa%2C+Mahmoud+Abou%22">Alaiwa, Mahmoud Abou</searchLink><br /><searchLink fieldCode="AR" term="%22Ernst%2C+Sarah+E%2E%22">Ernst, Sarah E.</searchLink><br /><searchLink fieldCode="AR" term="%22Karp%2C+Philip+H%2E%22">Karp, Philip H.</searchLink><br /><searchLink fieldCode="AR" term="%22Wohlford-Lenane%2C+Christine+L%2E%22">Wohlford-Lenane, Christine L.</searchLink><br /><searchLink fieldCode="AR" term="%22Heilmann%2C+Kristopher+P%2E%22">Heilmann, Kristopher P.</searchLink><br /><searchLink fieldCode="AR" term="%22Leidinger%2C+Mariah+R%2E%22">Leidinger, Mariah R.</searchLink><br /><searchLink fieldCode="AR" term="%22Allen%2C+Patrick+D%2E%22">Allen, Patrick D.</searchLink><br /><searchLink fieldCode="AR" term="%22Zabner%2C+Joseph%22">Zabner, Joseph</searchLink><br /><searchLink fieldCode="AR" term="%22McCray+Jr%2C+Paul+B%2E%22">McCray Jr, Paul B.</searchLink><br /><searchLink fieldCode="AR" term="%22Ostedgaard%2C+Lynda+S%2E%22">Ostedgaard, Lynda S.</searchLink><br /><searchLink fieldCode="AR" term="%22Stoltz%2C+David+A%2E%22">Stoltz, David A.</searchLink><br /><searchLink fieldCode="AR" term="%22Randak%2C+Christoph+O%2E%22">Randak, Christoph O.</searchLink><br /><searchLink fieldCode="AR" term="%22Welsh%2C+Michael+J%2E%22">Welsh, Michael J.</searchLink>
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  Data: <searchLink fieldCode="JN" term="%22Science+%28pre-March+2025%29%22">Science (pre-March 2025)</searchLink>. 1/29/2016, Vol. 351 Issue 6272, p503-507. 5p.
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  Data: <searchLink fieldCode="DE" term="%22Acidification%22">Acidification</searchLink><br /><searchLink fieldCode="DE" term="%22Cystic+fibrosis%22">Cystic fibrosis</searchLink><br /><searchLink fieldCode="DE" term="%22Laboratory+mice%22">Laboratory mice</searchLink><br /><searchLink fieldCode="DE" term="%22Bicarbonate+ions%22">Bicarbonate ions</searchLink><br /><searchLink fieldCode="DE" term="%22Genetic+mutation%22">Genetic mutation</searchLink>
– Name: Abstract
  Label: Abstract
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  Data: Cystic fibrosis (CF) is caused by mutations in the gene that encodes the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel. In humans and pigs, the loss of CFTR impairs respiratory host defenses, causing airway infection. But CF mice are spared. We found that in all three species, CFTR secreted bicarbonate into airway surface liquid. In humans and pigs lacking CFTR, unchecked H+ secretion by the nongastric H+/K+ adenosine triphosphatase (ATP12A) acidified airway surface liquid, which impaired airway host defenses. In contrast, mouse airways expressed little ATP12A and secreted minimal H+; consequently, airway surface liquid in CF and non-CF mice had similar pH. Inhibiting ATP12A reversed host defense abnormalities in human and pig airways. Conversely, expressing ATP12A in CF mouse airways acidified airway surface liquid, impaired defenses, and increased airway bacteria. These findings help explain why CF mice are protected from infection and nominate ATP12A as a potential therapeutic target for CF. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Science (pre-March 2025) is the property of American Association for the Advancement of Science and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=pbh&AN=112623587
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        Value: 10.1126/science.aad5589
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        Text: English
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        PageCount: 5
        StartPage: 503
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      – SubjectFull: Acidification
        Type: general
      – SubjectFull: Cystic fibrosis
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      – SubjectFull: Laboratory mice
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      – TitleFull: Airway acidification initiates host defense abnormalities in cystic fibrosis mice.
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