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The polymeric mucin Muc5ac is required for allergic airway hyperreactivity

Author

Listed:
  • Christopher M. Evans

    (University of Colorado School of Medicine)

  • Dorota S. Raclawska

    (University of Colorado School of Medicine)

  • Fani Ttofali

    (University of Colorado School of Medicine)

  • Deborah R. Liptzin

    (University of Colorado School of Medicine)

  • Ashley A. Fletcher

    (University of Colorado School of Medicine)

  • Daniel N. Harper

    (University of Colorado School of Medicine)

  • Maggie A. McGing

    (University of Colorado School of Medicine)

  • Melissa M. McElwee

    (University of Texas, MD Anderson Cancer Center)

  • Olatunji W. Williams

    (Pediatrics, Peyton Manning Children’s Hospital)

  • Elizabeth Sanchez

    (University of Texas, MD Anderson Cancer Center)

  • Michelle G. Roy

    (University of Texas, MD Anderson Cancer Center)

  • Kristen N. Kindrachuk

    (Immunopathogenesis Section, Program in Barrier Immunity and Repair, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Thomas A. Wynn

    (Immunopathogenesis Section, Program in Barrier Immunity and Repair, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Holger K. Eltzschig

    (University of Colorado School of Medicine)

  • Michael R. Blackburn

    (The University of Texas—Houston Medical School)

  • Michael J. Tuvim

    (University of Texas, MD Anderson Cancer Center)

  • William J. Janssen

    (University of Colorado School of Medicine
    National Jewish Health)

  • David A. Schwartz

    (University of Colorado School of Medicine)

  • Burton F. Dickey

    (University of Texas, MD Anderson Cancer Center)

Abstract

In asthma, airflow obstruction is thought to result primarily from inflammation-triggered airway smooth muscle (ASM) contraction. However, anti-inflammatory and smooth muscle-relaxing treatments are often temporary or ineffective. Overproduction of the mucin MUC5AC is an additional disease feature that, while strongly associated pathologically, is poorly understood functionally. Here we show that Muc5ac is a central effector of allergic inflammation that is required for airway hyperreactivity (AHR) to methacholine (MCh). In mice bred on two well-characterized strain backgrounds (C57BL/6 and BALB/c) and exposed to two separate allergic stimuli (ovalbumin and Aspergillus extract), genetic removal of Muc5ac abolishes AHR. Residual MCh responses are identical to unchallenged controls, and although inflammation remains intact, heterogeneous mucous occlusion decreases by 74%. Thus, whereas inflammatory effects on ASM alone are insufficient for AHR, Muc5ac-mediated plugging is an essential mechanism. Inhibiting MUC5AC may be effective for treating asthma and other lung diseases where it is also overproduced.

Suggested Citation

  • Christopher M. Evans & Dorota S. Raclawska & Fani Ttofali & Deborah R. Liptzin & Ashley A. Fletcher & Daniel N. Harper & Maggie A. McGing & Melissa M. McElwee & Olatunji W. Williams & Elizabeth Sanche, 2015. "The polymeric mucin Muc5ac is required for allergic airway hyperreactivity," Nature Communications, Nature, vol. 6(1), pages 1-11, May.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7281
    DOI: 10.1038/ncomms7281
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    Cited by:

    1. Renjini, Ammini & Swapna, Mohanachandran Nair Sindhu & Satheesh Kumar, Krishnan Nair & Sankararaman, Sankaranarayana Iyer, 2023. "Time series and mel frequency analyses of wet and dry cough signals: A neural net classification," Physica A: Statistical Mechanics and its Applications, Elsevier, vol. 626(C).

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