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Alveolar macrophages play an important role in chronic obstructive pulmonary disease (COPD) via production of matrix metalloproteinases (MMPs) and cathepsins as well as their inhibitors, tissue inhibitors of metalloproteinases (TIMPs) and cystatin C (CST3). We hypothesized that expression levels of these molecules by alveolar macrophages at baseline and after stimulation would be influenced by genotype and associated with COPD phenotypes.

Quantitative PCR and enzyme-linked immunosorbent assays/gelatin 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 DL,CO/VA and to FEV1/FVC after correction for multiple comparisons. The expression level of MMP12 protein stimulated with LPS was also inversely related to DL,CO/VA 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 FEV1% 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.