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A fungal protease allergen provokes airway hyper-responsiveness in asthma

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  • Nariman A. Balenga

    (Molecular Signal Transduction Section, Laboratory of Allergic Diseases, NIAID/NIH
    Present address: Division of General & Oncologic Surgery, Department of Surgery University of Maryland, School of Medicine 655 W. Baltimore St., Room 10-010 Baltimore, Maryland 21201, USA.)

  • Michael Klichinsky

    (Pulmonary, Airways Biology Initiative, University of Pennsylvania)

  • Zhihui Xie

    (Molecular Signal Transduction Section, Laboratory of Allergic Diseases, NIAID/NIH)

  • Eunice C. Chan

    (Molecular Signal Transduction Section, Laboratory of Allergic Diseases, NIAID/NIH)

  • Ming Zhao

    (Protein Chemistry, Research Technologies Branch, Twinbrook I)

  • Joseph Jude

    (Pulmonary, Airways Biology Initiative, University of Pennsylvania)

  • Michel Laviolette

    (Institut universitaire de cardiologie et pneumologie de Québec (Laval University))

  • Reynold A. Panettieri

    (Pulmonary, Airways Biology Initiative, University of Pennsylvania)

  • Kirk M. Druey

    (Molecular Signal Transduction Section, Laboratory of Allergic Diseases, NIAID/NIH)

Abstract

Asthma, a common disorder that affects >250 million people worldwide, is defined by exaggerated bronchoconstriction to inflammatory mediators including acetylcholine (ACh), bradykinin and histamine—also termed airway hyper-responsiveness. Nearly 10% of people with asthma have severe, treatment-resistant disease, which is frequently associated with immunoglobulin-E sensitization to ubiquitous fungi, typically Aspergillus fumigatus (Af). Here we show that a major Af allergen, Asp f13, which is a serine protease, alkaline protease 1 (Alp 1), promotes airway hyper-responsiveness by infiltrating the bronchial submucosa and disrupting airway smooth muscle (ASM) cell-extracellular matrix (ECM) interactions. Alp 1-mediated ECM degradation evokes pathophysiological RhoA-dependent Ca2+ sensitivity and bronchoconstriction. These findings support a pathogenic mechanism in asthma and other lung diseases associated with epithelial barrier impairment, whereby ASM cells respond directly to inhaled environmental allergens to generate airway hyper-responsiveness.

Suggested Citation

  • Nariman A. Balenga & Michael Klichinsky & Zhihui Xie & Eunice C. Chan & Ming Zhao & Joseph Jude & Michel Laviolette & Reynold A. Panettieri & Kirk M. Druey, 2015. "A fungal protease allergen provokes airway hyper-responsiveness in asthma," Nature Communications, Nature, vol. 6(1), pages 1-13, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7763
    DOI: 10.1038/ncomms7763
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