MATRIX METALLOPROTEINASE EXPRESSION AND PRODUCTION BY ALVEOLAR MACROPHAGES IN EMPHYSEMA

The aim of this study was to examine the hypothesis that alveolar macr ophages represent a significant source of matrix-degrading proteinases in the emphysematous lung. Macrophages from bronchoalveolar lavage fl uid of 10 patients with emphysema and 10 normal volunteers were mainta ined in vitro for 24 h and assessed semiquantitatively for mRNA transc ript levels of the matrix metalloproteinases (MMPs) gelatinases A and B, macrophage metalloelastase (MME), and interstitial collagenase. Rel ease of these MMPs into the culture medium and secretion of neutrophil elastaselike activity was also assessed. Elevated levels of mRNA tran scripts for gelatinase B (p < 0.0005) and interstitial collagenase (p < 0.0005) were observed in macrophages from emphysematous patients. In creased collagenase (p < 0.01) and neutrophil elastaselike activities (p < 0.001) were also measured in conditioned medium from patient macr ophages. With gelatinase B, complexed forms of the enzyme were secrete d by patient but not by control macrophages. No difference in transcri pt levels of gelatinase A or MME was observed between patient and cont rol samples, and neither enzyme was detected in macrophage-conditioned media from either group. These results directly demonstrate that alve olar macrophages from the emphysematous lung produce elevated quantiti es of matrix-degrading enzymes with both elastolytic and collagenolyti c activities.