A disintegrin and metalloproteinase 33 protein in patients with asthma: Relevance to airflow limitation.
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 FEV(1)% 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.
Lee
Ji-Yeon
JY
Genome Research Center for Allergy and Respiratory Diseases, Soonchunhyang University, Bucheon Hospital, Gyeonggi Do, Korea.
Park
Sung-Woo
SW
Chang
Hee Kyoung
HK
Kim
Ho Young
HY
Rhim
Taiyoun
T
Lee
June-Hyuk
JH
Jang
An-Soo
AS
Koh
Eun-Suk
ES
Park
Choon-Sik
CS
D051722:ADAM Proteins / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D001249:Asthma / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D001706:Biopsy; D015153:Blotting, Western; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002478:Cells, Cultured; D019483:Disintegrins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D005541:Forced Expiratory Volume / Q000502:physiology; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012313:RNA / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012720:Severity of Illness Index
D019483:Disintegrins; D012313:RNA; D051722:ADAM Proteins; C450441:ADAM33 protein, human