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MMP-12+ macrophages are also increased in BAL in smokers and those with patients with COPD.67 Furthermore MMP-12 can increase the expression of placenta growth factor (PGF), upregulating downstream signalling molecules of PGF and resulting in bronchial epithelial cell apoptosis and emphysema.68 AMs also produce elastolytic cysteine proteinases that have the capacity to cause significant lung destruction, particularly in an acidic environment.69 Cathepsin S is another potent elastase, with expression and activity found to be increased in current smokers.70 Cystatin C (CysC) is a major constitutive secretory product of AMs and is the most important inhibitor to cysteine proteinases which are also produced by the cells