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(Chest. 2001;120:S43.)
© 2001 American College of Chest Physicians

Gelatinolytic Activity in the BAL Fluid of Patients With Sarcoidosis*

Jesse Roman, MD; Howard Silverboard, MD; Rafael L. Perez, MD and Samuel M. Aguayo, MD, FCCP

* From the Atlanta Sarcoidosis Center, Department of Medicine, Division of Pulmonary and Critical Care Medicine, Atlanta VA Medical Center and Emory University School of Medicine, Atlanta, GA.

Correspondence to: Jesse Roman, MD, Associate Professor of Medicine, Emory University School of Medicine, Atlanta VA Medical Center, Pulmonary Room 12C 191, 1670 Clairmont Rd, Decatur, GA 30033

The detection of elevated levels of extracellular matrices in the lungs of sarcoidosis patients suggests that tissue remodeling plays a pathogenetic role in this disease. Activation of tissue remodeling in diseased human and animal lungs is often associated with increased expression of matrix-degrading enzymes with gelatinolytic activity. We hypothesized that pulmonary sarcoidosis triggers the increased expression of gelatinolytic activity detectable in BAL fluid. To test the hypothesis, we measured the gelatinolytic activity present in 35 samples of BAL fluid obtained from 32 patients with sarcoidosis using gelatin-zymography. We found that most (24 of 35 samples) but not all samples obtained from sarcoidosis lungs contained significant amounts of gelatinolytic activity as determined by densitometric scanning of the zymograms, whereas no activity was detected in the samples obtained from five healthy volunteers. Matrix metalloproteinase-9 appeared responsible for most of the gelatinolytic activity detected. A small but significant inverse correlation was found between the intensity of the gelatinolytic activity and several measures of pulmonary function, including FEV1 (r = -0.51; p = 0.002) and FVC (r = -0.49; p = 0.003). Patients with high levels of gelatinolytic activity had lower percent predicted values of FEV1 (p < 0.001), FVC (p < 0.0001), total lung capacity (p < 0.003), and diffusing capacity of the lung for carbon monoxide (p < 0.002) when compared to those with low levels of gelatinolytic activity. High levels of gelatinolytic activity also correlated with radiographic staging and the persistence of defects in pulmonary function tests long term. The data suggest that sarcoidosis triggers tissue remodeling with increased production of gelatinolytic activity in the lung and that this plays a pathogenetic role in the disease.





This Article
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