A disintegrin and metalloprotease (ADAM) 33 protein in patients with pulmonary sarcoidosis

Authors

  • ASIF SHAFFIQ,

    1. Division of Infection, Inflammation and Immunity, University of Southampton School of Medicine
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    • These authors contributed equally to this work.

  • HANS MICHAEL HAITCHI,

    1. Division of Infection, Inflammation and Immunity, University of Southampton School of Medicine
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    • These authors contributed equally to this work.

  • YUN YUNG PANG,

    1. Division of Infection, Inflammation and Immunity, University of Southampton School of Medicine
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  • ABDULLAH A. ALANGARI,

    1. Division of Infection, Inflammation and Immunity, University of Southampton School of Medicine
    2. Department of Paediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia
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  • MARK G. JONES,

    1. Division of Infection, Inflammation and Immunity, University of Southampton School of Medicine
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  • BEN G. MARSHALL,

    1. NIHR Respiratory Biomedical Research Unit, Southampton General Hospital, Southampton, Hampshire, UK
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  • PETER H. HOWARTH,

    1. Division of Infection, Inflammation and Immunity, University of Southampton School of Medicine
    2. NIHR Respiratory Biomedical Research Unit, Southampton General Hospital, Southampton, Hampshire, UK
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  • DONNA E. DAVIES,

    Corresponding author
    1. Division of Infection, Inflammation and Immunity, University of Southampton School of Medicine
    2. NIHR Respiratory Biomedical Research Unit, Southampton General Hospital, Southampton, Hampshire, UK
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  • KATHERINE M.A. O'REILLY

    1. NIHR Respiratory Biomedical Research Unit, Southampton General Hospital, Southampton, Hampshire, UK
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Donna E. Davies, Mailpoint 810, Level F, Sir Henry Wellcome Laboratories, South Block, Southampton General Hospital, Southampton SO16 6YD, UK. Email: donnad@soton.ac.uk

ABSTRACT

Background and objective: A disintegrin and metalloproteinase (ADAM) 33 is a susceptibility gene associated with inflammatory lung and skin diseases. It is selectively expressed in mesenchymal cells, and its metalloprotease activity has been linked to angiogenesis and tissue remodelling. A soluble form of ADAM33 (sADAM33) has been identified in the bronchoalveolar lavage fluid (BALF) of asthmatic patients, and its levels inversely correlate with lung function. Because of its association with inflammatory lung diseases, it was hypothesized that sADAM33 is elevated in BALF of patients with pulmonary sarcoidosis.

Methods:  After removal of Ig using Protein A/G and enrichment using Concanavalin A beads, sADAM33 was identified in BALF by Western blotting. A fluorescence resonance energy transfer peptide cleavage assay was used to assess ADAM33-like activity in BALF.

Results:  sADAM33 protein in BALF was detected as a 25 kDa fragment, and levels were significantly increased in samples from sarcoid patients when compared to healthy controls (P < 0.05). Levels of sADAM33 were inversely correlated with lung function (FVC%) (P < 0.05) and DLCO % predicted (P < 0.01). No difference in sADAM33 enzymatic activity was observed between healthy and sarcoid BALF samples.

Conclusions:  Release of sADAM33 is increased in sarcoid and may be associated with abnormal lung function. sADAM33 may be a biomarker of lung tissue inflammation and remodelling in sarcoid.

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