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Published ahead of print on December 30, 2005, doi:10.1164/rccm.200409-1175OC
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American Journal of Respiratory and Critical Care Medicine Vol 173. pp. 729-735, (2006)
© 2006 American Thoracic Society
doi: 10.1164/rccm.200409-1175OC


Original Article

A Disintegrin and Metalloproteinase 33 Protein in Patients with Asthma

Relevance to Airflow Limitation

Ji-Yeon Lee*, Sung-Woo Park*, Hee Kyoung Chang, Ho Young Kim, TaiYoun Rhim, June-Hyuk Lee, An-Soo Jang, Eun-Suk Koh and Choon-Sik Park

Genome Research Center for Allergy and Respiratory Diseases, Soonchunhyang University, Bucheon Hospital, Gyeonggi Do, Korea

Correspondence and requests for reprints should be addressed to Choon-Sik Park, M.D., Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University, Bucheon Hospital, 1174, Jung Dong, Wonmi Ku, Bucheon, Gyeonggi Do, 420-021, Korea. E-mail: mdcspark{at}unitel.co.kr

Background: ADAM33 has been identified as a novel asthma susceptibility gene in genomewide screening and association studies. High-level expression in smooth muscles and fibroblasts suggests that ADAM33 plays a role in airway remodeling in patients with asthma.

Methods: The ADAM33 protein was identified in the bronchoalveolar lavage (BAL) fluids of patients with asthma and normal control subjects using Western blotting antibody against the catalytic domain. ADAM33 expression was analyzed using immunohistochemical staining of mucosal biopsy specimens. The levels of ADAM33 protein in the BAL fluids were measured by dot blotting, and were correlated with the FEV1 values of the patients with asthma.

Results: Western blot analysis revealed the presence of the ADAM33 protein, with a molecular mass of approximately 55 kD in the BAL fluids. ADAM33 was expressed in the smooth muscles and basement membranes of almost all the patients with asthma, but was absent in the normal control subjects. The ADAM33 levels were increased significantly in patients with moderate to severe asthma and in patients with mild asthma, as compared with normal control subjects (p = 0.001 and p = 0.016, respectively). The ADAM33 protein levels correlated inversely with the FEV1% predicted in the patients with asthma (r = –0.486, p = 0.018).

Conclusions: ADAM33 is associated with asthma development, and the levels of ADAM protein are related to asthma severity.

Key Words: ADAM33 • airflow limitation • asthma • basement membrane • smooth muscle




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