Cathepsin D activity is increased in alveolar macrophages and bronchoalveolar lavage fluid of smokers

Am Rev Respir Dis. 1989 Oct;140(4):958-60. doi: 10.1164/ajrccm/140.4.958.


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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Bronchoalveolar Lavage Fluid / analysis
  • Bronchoalveolar Lavage Fluid / pathology*
  • Cathepsin D / metabolism*
  • Female
  • Humans
  • Leukocyte Count
  • Lymphocytes / cytology
  • Macrophages / cytology
  • Macrophages / enzymology*
  • Male
  • Middle Aged
  • Proteins / analysis
  • Pulmonary Alveoli / cytology*
  • Smoking / pathology*


  • Proteins
  • Cathepsin D