title: Sputum ADAM8 expression is increased in severe asthma and COPD.
abstract: BACKGROUND
  Severe asthma and chronic obstructive pulmonary disease (COPD) are chronic inflammatory airway diseases in which the mechanisms are not fully understood. A disintegrin and metalloproteinase domain 8 (ADAM8) is an enzyme expressed on most leucocytes and may be important for facilitating leucocyte migration in respiratory disease.
  
  
  OBJECTIVE
  To investigate ADAM8 mRNA and protein expression in asthma and COPD and its relationship between asthma severity and inflammatory phenotypes.
  
  
  METHODS
  Induced sputum was collected from 113 subjects with asthma (severe n = 31, uncontrolled n = 39 and controlled n = 35), 20 subjects with COPD and 21 healthy controls. Sputum ADAM8 mRNA expression was measured by qPCR, and soluble ADAM8 (sADAM8) protein was measured in the sputum supernatant by validated ELISA.
  
  
  RESULTS
  ADAM8 mRNA correlated with ADAM8 protein levels (r = 0.27, P < 0.01). ADAM8 mRNA (P = 0.004) and sADAM8 protein (P = 0.014) levels were significantly higher in both asthma and COPD compared with healthy controls. ADAM8 mRNA (P = 0.035) and sADAM8 protein (P = 0.002) levels were significantly higher in severe asthma compared with controlled asthma. Total inflammatory cell count (P < 0.01) and neutrophils (P < 0.01) were also elevated in severe asthmatic sputum. Although ADAM8 mRNA was significantly higher in eosinophilic and neutrophilic asthma (P < 0.001), sADAM8 did not differ between asthma inflammatory phenotypes. ADAM8 expression positively correlated with sputum total cell count and sputum neutrophils.
  
  
  CONCLUSIONS
  ADAM8 expression is increased in both severe asthma and COPD and associated with sputum total cell count and neutrophils. ADAM8 may facilitate neutrophil migration to the airways in severe asthma and COPD.
authors.affiliation: Virus Infections/Immunity Vaccines & Asthma, Hunter Medical Research Institute, New Lambton Heights, NSW, Australia; Priority Research Centre for Asthma and Respiratory Diseases, The University of Newcastle, Callaghan, NSW, Australia; Severe Asthma Network, Woolcock Institute of Medical Research, Glebe, NSW, Australia; The University of Sydney, Camperdown/Darlington, NSW, Australia.
authors.forename: K M
authors.initials: KM
authors.lastname: Oreo
authors.forename: P G
authors.initials: PG
authors.lastname: Gibson
authors.forename: J L
authors.initials: JL
authors.lastname: Simpson
authors.forename: L G
authors.initials: LG
authors.lastname: Wood
authors.forename: V M
authors.initials: VM
authors.lastname: McDonald
authors.forename: K J
authors.initials: KJ
authors.lastname: Baines
mesh_terms: D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism*; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage; D000328:Adult; D000368:Aged; D001249:Asthma / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D015870:Gene Expression; D006801:Humans; D016130:Immunophenotyping; D007958:Leukocyte Count; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012307:Risk Factors; D012720:Severity of Illness Index; D013183:Sputum / Q000378:metabolism*; D055815:Young Adult
chemical_list: D000305:Adrenal Cortex Hormones; D008565:Membrane Proteins; D012333:RNA, Messenger; D051722:ADAM Proteins; C068490:ADAM8 protein, human