title: Expression of matrix metalloproteinase-1 in alveolar macrophages, type II pneumocytes, and airways in smokers: relationship to lung function and emphysema.
abstract: BACKGROUND
  An imbalance between proteolytic enzymes and their inhibitors is thought to be involved in the pathogenesis of chronic obstructive pulmonary disease. Matrix metalloproteinase-1, also known as interstitial collagenase, has been implicated as a potentially important proteinase in the genesis of chronic obstructive pulmonary disease and, more specifically, emphysema.
  
  
  METHODS
  We performed quantitative immunohistochemical assessment of matrix metalloproteinase-1 expression in the resected lung of 20 smokers/ex-smokers who had varying severity of airflow obstruction and emphysema and compared this with the lungs of 5 nonsmokers. Emphysema was measured using a morphometric measure of the lungs' surface area/volume ratio and with qualitative and quantitative computed tomography (CT) measures of emphysema.
  
  
  RESULTS
  There were significantly more matrix metalloproteinase-1-expressing alveolar macrophages and type II pneumocytes as well as a greater percentage of small airways that stained positively for matrix metalloproteinase-1 in the lungs of smokers than in those of nonsmokers (p < 0.0001, p < 0.0001, and p = 0.0003, respectively). The extent of staining of type II pneumocytes and airways for matrix metalloproteinase-1 was significantly related to the extent of smoking (p = 0.012 and p = 0.013, respectively). In addition, the extent of matrix metalloproteinase-1 staining of alveolar macrophages was related to the lung surface area/volume ratio and to qualitative estimates of emphysema on CT.
  
  
  CONCLUSIONS
  These findings suggest that cigarette smoking increases expression of matrix metalloproteinase-1 in alveolar macrophages as well as in alveolar and small airway epithelial cells. Smokers who develop emphysema have increased alveolar macrophage expression of matrix metalloproteinase-1.
authors.affiliation: St. Paul's Hospital, University of British Columbia Center for Heart Lung Innovation, 166 - 1081 Burrard Street, Vancouver, BC, V6Z 1Y6, Canada.
authors.forename: Alison M
authors.initials: AM
authors.lastname: Wallace
authors.forename: Leanna B
authors.initials: LB
authors.lastname: Loy
authors.forename: Raja T
authors.initials: RT
authors.lastname: Abboud
authors.forename: Jeanine M
authors.initials: JM
authors.lastname: D'Armiento
authors.forename: Harvey O
authors.initials: HO
authors.lastname: Coxson
authors.forename: Nestor L
authors.initials: NL
authors.lastname: Muller
authors.forename: Steve
authors.initials: S
authors.lastname: Kalloger
authors.forename: Xing
authors.initials: X
authors.lastname: Li
authors.forename: W
authors.initials: W
authors.lastname: Mark Elliott
authors.forename: John C
authors.initials: JC
authors.lastname: English
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Finley
authors.forename: Peter D
authors.initials: PD
authors.lastname: Paré
mesh_terms: D000328:Adult; D000368:Aged; D056809:Alveolar Epithelial Cells / Q000201:enzymology*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008168:Lung / Q000000981:diagnostic imaging / Q000201:enzymology* / Q000503:physiopathology; D016676:Macrophages, Alveolar / Q000201:enzymology*; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000032:analysis*; D008875:Middle Aged; D011656:Pulmonary Emphysema / Q000000981:diagnostic imaging / Q000201:enzymology* / Q000209:etiology / Q000503:physiopathology; D012129:Respiratory Function Tests; D012720:Severity of Illness Index; D012907:Smoking / Q000009:adverse effects / Q000378:metabolism* / Q000503:physiopathology; D014057:Tomography, X-Ray Computed; D015854:Up-Regulation
chemical_list: C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1