A Disintegrin and Metalloproteinase 33 Protein in Patients with Asthma: Relevance to Airflow Limitation

• Published in: American journal of respiratory and critical care medicine Vol. 173; no. 7; pp. 729 - 735
• Main Authors: Lee, Ji-Yeon, Park, Sung-Woo, Chang, Hee Kyoung, Kim, Ho Young, Rhim, TaiYoun, Lee, June-Hyuk, Jang, An-Soo, Koh, Eun-Suk, Park, Choon-Sik
• Format: Journal Article
• Language: English
• Published: New York, NY Am Thoracic Soc 01.04.2006; American Lung Association; American Thoracic Society
• Subjects: ADAM Proteins - genetics; ADAM Proteins - metabolism; Adult; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Asthma - metabolism; Asthma - pathology; Asthma - physiopathology; Biological and medical sciences; Biopsy; Blotting, Western; Bronchoalveolar Lavage Fluid - chemistry; Bronchoalveolar Lavage Fluid - cytology; Cells, Cultured; Clinical death. Palliative care. Organ gift and preservation; Disintegrins - genetics; Disintegrins - metabolism; Female; Fibroblasts - metabolism; Fibroblasts - pathology; Forced Expiratory Volume - physiology; Gene Expression; Humans; Immunohistochemistry; Intensive care medicine; Investigative techniques of respiratory function; Investigative techniques, diagnostic techniques (general aspects); Male; Medical sciences; Middle Aged; Prognosis; Reverse Transcriptase Polymerase Chain Reaction; RNA - genetics; Severity of Illness Index; Human; Lung disease; Intensive care; Respiratory disease; ADAM33; airflow limitation; Bronchus disease; Smooth muscle; Obstructive pulmonary disease; Resuscitation; Asthma; Basement membrane
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/rccm.200409-1175OC

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. 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. 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 FEV(1)% predicted in the patients with asthma (r = -0.486, p = 0.018). ADAM33 is associated with asthma development, and the levels of ADAM protein are related to asthma severity.