title: A disintegrin and metalloprotease (ADAM) 33 protein in patients with pulmonary sarcoidosis.
abstract: OBJECTIVE
  A disintegrin and metalloproteinase (ADAM) 33 is a susceptibility gene associated with inflammatory lung and skin diseases. It is selectively expressed in mesenchymal cells, and its metalloprotease activity has been linked to angiogenesis and tissue remodelling. A soluble form of ADAM33 (sADAM33) has been identified in the bronchoalveolar lavage fluid (BALF) of asthmatic patients, and its levels inversely correlate with lung function. Because of its association with inflammatory lung diseases, it was hypothesized that sADAM33 is elevated in BALF of patients with pulmonary sarcoidosis.
  
  
  METHODS
  After removal of Ig using Protein A/G and enrichment using Concanavalin A beads, sADAM33 was identified in BALF by Western blotting. A fluorescence resonance energy transfer peptide cleavage assay was used to assess ADAM33-like activity in BALF.
  
  
  RESULTS
  sADAM33 protein in BALF was detected as a 25 kDa fragment, and levels were significantly increased in samples from sarcoid patients when compared to healthy controls (P < 0.05). Levels of sADAM33 were inversely correlated with lung function (FVC%) (P < 0.05) and DL(CO) % predicted (P < 0.01). No difference in sADAM33 enzymatic activity was observed between healthy and sarcoid BALF samples.
  
  
  CONCLUSIONS
  Release of sADAM33 is increased in sarcoid and may be associated with abnormal lung function. sADAM33 may be a biomarker of lung tissue inflammation and remodelling in sarcoid.
authors: Division of Infection, Inflammation and Immunity, University of Southampton School of Medicine, Southampton, Hampshire, UK.
authors: Asif
authors: A
authors: Shaffiq
authors: Hans Michael
authors: HM
authors: Haitchi
authors: Yun Yung
authors: YY
authors: Pang
authors: Abdullah A
authors: AA
authors: Alangari
authors: Mark G
authors: MG
authors: Jones
authors: Ben G
authors: BG
authors: Marshall
authors: Peter H
authors: PH
authors: Howarth
authors: Donna E
authors: DE
authors: Davies
authors: Katherine M A
authors: KM
authors: O'Reilly
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism*; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D001999:Bronchoscopy; D003937:Diagnosis, Differential; D005260:Female; D031541:Fluorescence Resonance Energy Transfer / Q000379:methods; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008853:Microscopy; D008875:Middle Aged; D017565:Sarcoidosis, Pulmonary / Q000175:diagnosis / Q000201:enzymology*; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; D051722:ADAM Proteins; C499566:ADAM3A protein, human