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.
The capacity of alveolar macrophages (AM) obtained from smokers and nonsmokers to secrete cathepsin B and its inhibitor cystatin C was examined because of the concept that an imbalance in the production of proteolytic enzymes and/or their inhibitors could be responsible for the lung damage seen in smokers. Quantitation of immunoprecipitates on Western blots showed that the amount of total cystatin C secreted into the culture medium by AM of smokers was significantly greater than the amount secreted by cells obtained from nonsmokers, whereas the difference between the amount of cathepsin B secreted by the AM of smokers and that from nonsmokers did not appear significant. The cystatin C found in the medium conditioned by AM of nonsmokers appeared to be more heterogeneous in molecular size, presenting either as a single band of about 14 Kd or as a high-molecular-weight triplet of about 69 Kd, 63 Kd, and 57.3 Kd. Furthermore, in some cases there were single or doublet bands at 14 Kd as well as the high-molecular-weight triplets. In contrast, smokers AM-conditioned medium uniformly possessed both the low-and the high-molecular-weight cystatin C. Cathepsin B was not detected in Western blots at its reported molecular weights but was identified at the exact area occupied by the higher molecular weight cystatin C, i.e., at bands corresponding to 69 Kd, 63 Kd, and 57.3 Kd. Therefore, it is clear that in culture media of AM, cystatin C and cathepsin B are present as proteinase-antiproteinase complexes. The observation also suggests that in smokers an excess of cystatin C may be elaborated, which, if further substantiated, would show for the first time a likely role for this proteinase inhibitor in vivo.
Pulmonary edema is known to develop in users of heroin and methadone. Its association with cocaine use is usually a postmortem finding. There has been only 1 report of pulmonary edema being diagnosed clinically after cocaine use. In that case the cocaine was used intravenously, and death occurred within 3 h after the onset of symptoms. Here we describe a patient who developed acute pulmonary edema after smoking "freebase" cocaine. The pulmonary edema resolved spontaneously within 72 h. The cause of the acute reversible pulmonary edema was probably related to both pressure- and permeability-related changes.
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