Cathepsin D activity is increased in alveolar macrophages and bronchoalveolar lavage fluid of smokers.
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(0-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 less than 0.001) and approximately seven times higher in BALF from smokers than from nonsmokers (3,620 +/- 490 versus 515 +/- 165; p less than 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.
Chang
J C
JC
Veterans Administration Medical Center, Bronx, NY 10468.
Yoo
O H
OH
Lesser
M
M
D000328:Adult; D001992:Bronchoalveolar Lavage Fluid / Q000032:analysis / Q000473:pathology*; D002402:Cathepsin D / Q000378:metabolism*; D005260:Female; D006801:Humans; D007958:Leukocyte Count; D008214:Lymphocytes / Q000166:cytology; D008264:Macrophages / Q000166:cytology / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D011506:Proteins / Q000032:analysis; D011650:Pulmonary Alveoli / Q000166:cytology*; D012907:Smoking / Q000473:pathology*
D011506:Proteins; D002402:Cathepsin D