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.

[1]  D. Postma,et al.  A disintegrin and metalloprotease 33 polymorphisms and lung function decline in the general population. , 2005 .

[2]  A. Woodcock,et al.  Polymorphisms in a disintegrin and metalloprotease 33 (ADAM33) predict impaired early-life lung function. , 2005, American journal of respiratory and critical care medicine.

[3]  David I. Wilson,et al.  ADAM33 expression in asthmatic airways and human embryonic lungs. , 2005, American journal of respiratory and critical care medicine.

[4]  E. Silverman,et al.  ADAM33 polymorphisms and phenotype associations in childhood asthma. , 2004, The Journal of allergy and clinical immunology.

[5]  H. Shin,et al.  ADAM33 polymorphism: association with bronchial hyper‐responsiveness in Korean asthmatics , 2004, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[6]  D. Postma,et al.  Polymorphisms of the ADAM33 gene are associated with accelerated lung function decline in asthma , 2004, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[7]  Jun Zou,et al.  Catalytic Activity of Human ADAM33* , 2004, Journal of Biological Chemistry.

[8]  S. Holgate,et al.  The splicing and fate of ADAM33 transcripts in primary human airways fibroblasts. , 2004, American journal of respiratory cell and molecular biology.

[9]  H. Gohlke,et al.  Asthma is associated with single‐nucleotide polymorphisms in ADAM33 , 2004, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[10]  S. Holgate,et al.  The role of ADAM33 in the pathogenesis of asthma , 2004, Springer Seminars in Immunopathology.

[11]  P. Kwok,et al.  ADAM33 is not associated with asthma in Puerto Rican or Mexican populations. , 2003, American journal of respiratory and critical care medicine.

[12]  D. Postma,et al.  Association of a disintegrin and metalloprotease 33 (ADAM33) gene with asthma in ethnically diverse populations. , 2003, The Journal of allergy and clinical immunology.

[13]  Jun Zou,et al.  Human ADAM33 messenger RNA expression profile and post-transcriptional regulation. , 2003, American journal of respiratory cell and molecular biology.

[14]  S. Holgate,et al.  Airway remodeling in asthma: new insights. , 2003, The Journal of allergy and clinical immunology.

[15]  Jun Zou,et al.  Human ADAM33: protein maturation and localization. , 2003, Biochemical and biophysical research communications.

[16]  Steuart Rorke,et al.  Association of the ADAM33 gene with asthma and bronchial hyperresponsiveness , 2002, Nature.

[17]  K. Yoshino,et al.  Identification and characterization of novel mouse and human ADAM33s with potential metalloprotease activity. , 2002, Gene.

[18]  R. Djukanović,et al.  The contribution of interleukin (IL)-4 and IL-13 to the epithelial-mesenchymal trophic unit in asthma. , 2001, American journal of respiratory cell and molecular biology.

[19]  F. Aksoy,et al.  Ultrastructural examination of bronchial biopsy specimens from children with moderate asthma , 2001, Thorax.

[20]  W. Busse,et al.  Pathophysiology of severe asthma. , 2000, The Journal of allergy and clinical immunology.

[21]  M. Kitaichi,et al.  Increased levels of interleukin-6 are associated with lymphocytosis in bronchoalveolar lavage fluids of idiopathic nonspecific interstitial pneumonia. , 2000, American journal of respiratory and critical care medicine.

[22]  P. Slocombe,et al.  Meltrin gamma(ADAM-9) mediates cellular adhesion through alpha(6)beta(1 )integrin, leading to a marked induction of fibroblast cell motility. , 2000, Journal of cell science.

[23]  P. Primakoff,et al.  The ADAM gene family: surface proteins with adhesion and protease activity. , 2000, Trends in genetics : TIG.

[24]  Michael R. Kroeger,et al.  Structure–Function Analysis of the ADAM Family of Disintegrin-Like and Metalloproteinase-Containing Proteins (Review) , 1999, Journal of protein chemistry.

[25]  E. Mekada,et al.  A metalloprotease–disintegrin, MDC9/meltrin‐γ/ADAM9 and PKCδ are involved in TPA‐induced ectodomain shedding of membrane‐anchored heparin‐binding EGF‐like growth factor , 1998, The EMBO journal.

[26]  David C. Lee,et al.  An essential role for ectodomain shedding in mammalian development. , 1998, Science.

[27]  R. Black,et al.  ADAMs: focus on the protease domain. , 1998, Current opinion in cell biology.

[28]  P. Jeffery.  Structural alterations and inflammation of bronchi in asthma. , 1998, International journal of clinical practice. Supplement.

[29]  M. Lambert,et al.  Cloning of a disintegrin metalloproteinase that processes precursor tumour-necrosis factor-α , 1997, Nature.

[30]  Nicole Nelson,et al.  A metalloproteinase disintegrin that releases tumour-necrosis factor-α from cells , 1997, Nature.

[31]  A. James,et al.  The structure of large and small airways in nonfatal and fatal asthma. , 1993, The American review of respiratory disease.

[32]  P. Paré,et al.  A model of airway narrowing in asthma and in chronic obstructive pulmonary disease. , 1992, The American review of respiratory disease.

[33]  P. Howarth,et al.  Myofibroblasts and subepithelial fibrosis in bronchial asthma. , 1990, American journal of respiratory cell and molecular biology.

[34]  J. Hogg,et al.  A model of the mechanics of airway narrowing. , 1990, Journal of applied physiology.