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

A disintegrin and metalloprotease (ADAM) 33 protein in patients with pulmonary sarcoidosis
A disintegrin and metalloprotease (ADAM) 33 protein in patients with pulmonary sarcoidosis
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
a disintegrin and metalloproteinase protein, biological marker, inflammation, remodelling, sarcoidosis
1323-7799
342-349
Shaffiq, Asif
75396644-de1a-4456-a24d-25f7e1f1c91f
Haitchi, Hans Michael
68dadb29-305d-4236-884f-e9c93f4d78fe
Pang, Yun Yung
df1c3d15-af37-46d3-8743-89e849425d65
Alangari, Abdullah A.
f2d7f1fb-6191-44e6-8049-745a62de6e5d
Jones, Mark G.
a6fd492e-058e-4e84-a486-34c6035429c1
Marshall, Ben G.
12be7650-0780-4923-8c8d-e26862fe3213
Howarth, Peter H.
ff19c8c4-86b0-4a88-8f76-b3d87f142a21
Davies, Donna E.
7de8fdc7-3640-4e3a-aa91-d0e03f990c38
O'Reilly, Katherine M.A.
6c323cd0-0c68-4913-9666-7e4f655b816f
Shaffiq, Asif
75396644-de1a-4456-a24d-25f7e1f1c91f
Haitchi, Hans Michael
68dadb29-305d-4236-884f-e9c93f4d78fe
Pang, Yun Yung
df1c3d15-af37-46d3-8743-89e849425d65
Alangari, Abdullah A.
f2d7f1fb-6191-44e6-8049-745a62de6e5d
Jones, Mark G.
a6fd492e-058e-4e84-a486-34c6035429c1
Marshall, Ben G.
12be7650-0780-4923-8c8d-e26862fe3213
Howarth, Peter H.
ff19c8c4-86b0-4a88-8f76-b3d87f142a21
Davies, Donna E.
7de8fdc7-3640-4e3a-aa91-d0e03f990c38
O'Reilly, Katherine M.A.
6c323cd0-0c68-4913-9666-7e4f655b816f

Shaffiq, Asif, Haitchi, Hans Michael, Pang, Yun Yung, Alangari, Abdullah A., Jones, Mark G., Marshall, Ben G., Howarth, Peter H., Davies, Donna E. and O'Reilly, Katherine M.A. (2012) A disintegrin and metalloprotease (ADAM) 33 protein in patients with pulmonary sarcoidosis. Respirology, 17 (2), 342-349. (doi:10.1111/j.1440-1843.2011.02098.x). (PMID:22040125)

Record type: Article

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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e-pub ahead of print date: 24 January 2012
Published date: February 2012
Keywords: a disintegrin and metalloproteinase protein, biological marker, inflammation, remodelling, sarcoidosis
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 337448
URI: http://eprints.soton.ac.uk/id/eprint/337448
ISSN: 1323-7799
PURE UUID: a055b596-4734-4bb9-a0d9-e25180b349cc
ORCID for Hans Michael Haitchi: ORCID iD orcid.org/0000-0001-8603-302X
ORCID for Mark G. Jones: ORCID iD orcid.org/0000-0001-6308-6014
ORCID for Donna E. Davies: ORCID iD orcid.org/0000-0002-5117-2991

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Date deposited: 26 Apr 2012 09:18
Last modified: 15 Mar 2024 03:29

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Contributors

Author: Asif Shaffiq
Author: Yun Yung Pang
Author: Abdullah A. Alangari
Author: Mark G. Jones ORCID iD
Author: Ben G. Marshall
Author: Donna E. Davies ORCID iD
Author: Katherine M.A. O'Reilly

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