Expression of a metalloproteinase that degrades native type V collagen and denatured collagens by cultured human alveolar macrophages.

Human pulmonary alveolar macrophages obtained by bronchoalveolar lavage from both normal controls and smokers secreted in vitro a neutral proteinase that degraded denatured collagens. Optimal expression of the proteinase was detected after 3-5 d of culture. The proteinase could not be detected in the media of cultures that had been treated with 0.5 micrograms/ml of cycloheximide. The gelatinase had an Mr of 90,000 and was immunologically cross-reactive with human neutrophil gelatinase. When newly synthesized 35S-methionine-labeled proteins were analyzed, the proteinase appeared to be a major secretion product of alveolar macrophages. Chromatography on gelatin-Sepharose gave a single peak of activity that was predominantly composed of the 90,000-mol-wt proteinase. The proteolytic activity in the gelatin-Sepharose-purified material was inhibited by EDTA and 1,10-phenanthroline, but not by N-ethylmaleimide or phenylmethanesulfonyl fluoride, indicating that the proteinase was a metalloproteinase. The partially purified material was also capable of degrading native type V collagen and this degradation was inhibited in the presence of an antibody to neutrophil gelatinase. The data suggest that human alveolar macrophages in culture elaborate a metalloproteinase that degrades both native type V collagen and denatured collagens.