title: Alveolar macrophage proteinase/antiproteinase expression in lung function and emphysema.
abstract: Alveolar macrophages play an important role in chronic obstructive pulmonary disease via production of matrix metalloproteinases (MMPs) and cathepsins as well as their inhibitors, tissue inhibitors of metalloproteinases and cystatin C. We hypothesised that expression levels of these molecules by alveolar macrophages at baseline and after stimulation would be influenced by genotype and associated with chronic obstructive pulmonary disease phenotypes. Quantitative PCR and ELISAs/gelatine zymography were used to investigate expression levels of mRNA and protein, respectively. The relationships of expression with genotype, pulmonary function and emphysema were analysed. The results showed that basal expression level of MMP12 mRNA was inversely related to the diffusing capacity of the lung for carbon monoxide/alveolar volume and to forced expiratory volume in 1 s/forced vital capacity after correction for multiple comparisons. The expression level of MMP12 protein stimulated with lipopolysaccharide was also inversely related to the diffusing capacity of the lung for carbon monoxide/alveolar volume and was positively related to the extent of emphysema. The basal expression of MMP1 mRNA was positively correlated with the extent of emphysema. Cathepsin L protein level was positively associated with forced expiratory volume in 1 s % predicted. We conclude that increased MMP12 and MMP1 expression may play a role in the pathogenesis of emphysema. Cathepsin L and MMP9 may be involved in the development of airflow limitation.
authors.affiliation: Institute for Heart and Lung Health, St. Paul's Hospital, Vancouver, BC.
authors.forename: Takeo
authors.initials: T
authors.lastname: Ishii
authors.forename: Raja T
authors.initials: RT
authors.lastname: Abboud
authors.forename: Alison M
authors.initials: AM
authors.lastname: Wallace
authors.forename: John C
authors.initials: JC
authors.lastname: English
authors.forename: Harvey O
authors.initials: HO
authors.lastname: Coxson
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Finley
authors.forename: Karey
authors.initials: K
authors.lastname: Shumansky
authors.forename: Peter D
authors.initials: PD
authors.lastname: Paré
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Sandford
mesh_terms: D000368:Aged; D056668:Cathepsin L / Q000235:genetics* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005541:Forced Expiratory Volume; D020869:Gene Expression Profiling; D006801:Humans; D008168:Lung / Q000201:enzymology / Q000378:metabolism*; D016676:Macrophages, Alveolar / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics* / Q000378:metabolism; D053508:Matrix Metalloproteinase 12 / Q000235:genetics* / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D011653:Pulmonary Diffusing Capacity; D011656:Pulmonary Emphysema / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology; D012333:RNA, Messenger / Q000032:analysis*; D060888:Real-Time Polymerase Chain Reaction; D012720:Severity of Illness Index; D014797:Vital Capacity
chemical_list: D012333:RNA, Messenger; C534281:CTSL protein, human; D056668:Cathepsin L; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; C507122:MMP12 protein, human; D053508:Matrix Metalloproteinase 12; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1