Cathepsin D Activity Is Increased in Alveolar Macrophages and Bronchoalveolar Lavage Fluid of Smokers

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Abstract
Cathepsin D activity was determined in alveolar macrophages (AM) and cell-free bronchoalveolar lavage fluid (BALF) from volunteers who were current cigarette smokers and compared with that found in lifetime nonsmokers. Enzyme activity was determined with a highly sensitive and specific substrate [D-Phe-Ser(O-CH2-C6H5)-Phe-Phe-Ala-Ala-pAB]. Specific activity was more than three times higher in AM from smokers than in cells from nonsmokers (37,880 .+-. 2,090 versus 10,300 .+-. 1,200; p < 0.001) and approximately seven times higher in BALF from smokers than from nonsmokers (3,620 .+-. 490 versus 515 .+-. 165; p < 0.001). This study demonstrated that cigarette smoke is a potent inducer of cathepsin D activity in AM in vivo. Because cathepsin D is capable of degrading a variety of proteins, the finding of high concentrations of the enzyme in AM and BALF from smokers, along with previous observations of elevated cathepsin B activity, suggests that lysosomal enzymes may cause or contribute to structural lung damage associated with cigarette smoking.