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ADAM33 expression in asthmatic airways and human embryonic lungs

ADAM33 expression in asthmatic airways and human embryonic lungs
ADAM33 expression in asthmatic airways and human embryonic lungs
Rationale: Polymorphic variation in ADAM33 (A Disintegrin And Metalloprotease) is strongly associated with asthma and bronchial hyperresponsiveness in different populations. Objective and Methods: To study the role of ADAM33 in asthma, we investigated its expression in normal, asthmatic, and embryonic airways using reverse transcriptase–quantitative polymerase chain reaction and immunochemistry. Results: Several ADAM33 mRNA splice variants were detected in bronchial biopsies and embryonic lung; however, the β-isoform and variants encoding the metalloprotease domain were rare transcripts. Western blotting of bronchial biopsies confirmed the presence of multiple isoforms of ADAM33, which had molecular weights of 22, 37, 55, and 65 kD. Immunohistochemistry and laser confocal microscopy of adult bronchial biopsies showed that α–smooth muscle actin and ADAM33 immunoreactivity were mostly colocalized to smooth muscle and isolated cells in the submucosa. There was no significant difference in ADAM33 mRNA amplicons or protein in subjects with asthma compared with control subjects. In developing lung, ADAM33 was found around bronchial tubes; however, immunoreactivity was more widely distributed than α–smooth muscle actin within undifferentiated mesenchyme; on Western blots, an additional 25-kD ADAM33 variant was detected. Conclusions: Several ADAM33 protein isoforms occur in adult bronchial smooth muscle and in human embryonic bronchi and surrounding mesenchyme, strongly suggesting its importance in smooth muscle development and/or function, which could explain its genetic association with bronchial hyperresponsiveness. The occurrence of ADAM33 in embryonic mesenchymal cells suggests that it may be involved in airway wall “modeling” that contributes to the early life origins of asthma.
bronchial hyperresponsiveness, epithelial mesenchymal trophic unit, lung development, mesenchymal cells, remodeling
1073-449X
958-965
Haitchi, Hans Michael
68dadb29-305d-4236-884f-e9c93f4d78fe
Powell, Robert M.
884d6594-3f50-4be5-9516-d64b29dad63d
Shaw, Timothy J.
9bc1670c-4068-4689-9999-f06e96affde0
Howarth, Peter H.
ff19c8c4-86b0-4a88-8f76-b3d87f142a21
Wilson, Susan J.
21c6875d-6870-441b-ae7a-603562a646b8
Wilson, David I.
1500fca1-7082-4271-95f4-691f1d1252a2
Holgate, Stephen T.
2e7c17a9-6796-436e-8772-1fe6d2ac5edc
Davies, Donna E.
7de8fdc7-3640-4e3a-aa91-d0e03f990c38
Haitchi, Hans Michael
68dadb29-305d-4236-884f-e9c93f4d78fe
Powell, Robert M.
884d6594-3f50-4be5-9516-d64b29dad63d
Shaw, Timothy J.
9bc1670c-4068-4689-9999-f06e96affde0
Howarth, Peter H.
ff19c8c4-86b0-4a88-8f76-b3d87f142a21
Wilson, Susan J.
21c6875d-6870-441b-ae7a-603562a646b8
Wilson, David I.
1500fca1-7082-4271-95f4-691f1d1252a2
Holgate, Stephen T.
2e7c17a9-6796-436e-8772-1fe6d2ac5edc
Davies, Donna E.
7de8fdc7-3640-4e3a-aa91-d0e03f990c38

Haitchi, Hans Michael, Powell, Robert M., Shaw, Timothy J., Howarth, Peter H., Wilson, Susan J., Wilson, David I., Holgate, Stephen T. and Davies, Donna E. (2005) ADAM33 expression in asthmatic airways and human embryonic lungs. American Journal of Respiratory and Critical Care Medicine, 171 (9), 958-965. (doi:10.1164/rccm.200409-1251OC).

Record type: Article

Abstract

Rationale: Polymorphic variation in ADAM33 (A Disintegrin And Metalloprotease) is strongly associated with asthma and bronchial hyperresponsiveness in different populations. Objective and Methods: To study the role of ADAM33 in asthma, we investigated its expression in normal, asthmatic, and embryonic airways using reverse transcriptase–quantitative polymerase chain reaction and immunochemistry. Results: Several ADAM33 mRNA splice variants were detected in bronchial biopsies and embryonic lung; however, the β-isoform and variants encoding the metalloprotease domain were rare transcripts. Western blotting of bronchial biopsies confirmed the presence of multiple isoforms of ADAM33, which had molecular weights of 22, 37, 55, and 65 kD. Immunohistochemistry and laser confocal microscopy of adult bronchial biopsies showed that α–smooth muscle actin and ADAM33 immunoreactivity were mostly colocalized to smooth muscle and isolated cells in the submucosa. There was no significant difference in ADAM33 mRNA amplicons or protein in subjects with asthma compared with control subjects. In developing lung, ADAM33 was found around bronchial tubes; however, immunoreactivity was more widely distributed than α–smooth muscle actin within undifferentiated mesenchyme; on Western blots, an additional 25-kD ADAM33 variant was detected. Conclusions: Several ADAM33 protein isoforms occur in adult bronchial smooth muscle and in human embryonic bronchi and surrounding mesenchyme, strongly suggesting its importance in smooth muscle development and/or function, which could explain its genetic association with bronchial hyperresponsiveness. The occurrence of ADAM33 in embryonic mesenchymal cells suggests that it may be involved in airway wall “modeling” that contributes to the early life origins of asthma.

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More information

Published date: 2005
Keywords: bronchial hyperresponsiveness, epithelial mesenchymal trophic unit, lung development, mesenchymal cells, remodeling

Identifiers

Local EPrints ID: 24735
URI: http://eprints.soton.ac.uk/id/eprint/24735
ISSN: 1073-449X
PURE UUID: 974fc1f7-bd36-422b-944c-0e71e3b32b7d
ORCID for Hans Michael Haitchi: ORCID iD orcid.org/0000-0001-8603-302X
ORCID for Susan J. Wilson: ORCID iD orcid.org/0000-0003-1305-8271
ORCID for Donna E. Davies: ORCID iD orcid.org/0000-0002-5117-2991

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Date deposited: 03 Apr 2006
Last modified: 16 Mar 2024 03:29

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Contributors

Author: Robert M. Powell
Author: Timothy J. Shaw
Author: Susan J. Wilson ORCID iD
Author: David I. Wilson
Author: Donna E. Davies ORCID iD

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