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Published ahead of print on December 30, 2005, doi:10.1164/rccm.200409-1175OC

Am. J. Respir. Crit. Care Med., Volume 173, Number 7, April 2006, 729-735

A more recent version of this article appeared on April 1, 2006
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Submitted on September 7, 2004
Accepted on December 21, 2005

A Disintegrin and Metalloproteinase 33 Protein in Asthmatics : Relevance to Airflow Limitation

Ji-Yeon Lee1, Sung-Woo Park1, Hee Kyoung Chang1, Ho Young Kim1, TaiYoun Rhim1, June-Hyuk Lee1, An-Soo Jang1, Eun-Suk Koh1, and Choon-Sik Park1*

1 Department of Internal Medicine, Division of Allergy and Respiratory Medicine, Soonchunhyang University Bucheon Hospital, Genome Research Center for Allergy and Respiratory Diseases, Bucheon, Gyeonggi Do, Korea, Republic of

* To whom correspondence should be addressed. E-mail: mdcspark{at}unitel.co.kr.

Background: ADAM33 has been identified as a novel asthma susceptibility gene in genome-wide screening and association studies. High-level expression in smooth muscles and fibroblasts suggest that ADAM33 plays a role in airway remodeling in asthmatics. Methods: The ADAM33 protein was identified in the BAL fluids of asthmatics and normal controls 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 asthmatics. Results: Western blot analysis revealed the presence of the ADAM33 protein with a molecular mass of approximately 55kDa in the BAL fluids. ADAM33 was expressed in the smooth muscles and basement membranes of almost all the asthmatics, but was absent in the normal controls. The ADAM33 levels were increased significantly in moderate-to-severe asthmatics and in mild asthmatics, as compared to normal control subjects (p= 0.001 and p=0.016, respectively). The ADAM33 protein levels correlated inversely with the FEV1 % pred. in the asthmatics (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, asthma, airflow limitation, smooth muscle, basement membrane




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