CLONING AND CHARACTERIZATION OF A UNIQUE ELASTOLYTIC METALLOPROTEINASE PRODUCED BY HUMAN ALVEOLAR MACROPHAGES

Human alveolar macrophages have the capacity to degrade elastin. As an approach to define proteinases responsible for this activity, we rece ntly cloned a murine macrophage elastase cDNA and demonstrated that it is a member of the matrix metalloproteinase gene family (Shapiro, S. D., Griffin, G. L., Gilbert, D. J., Jenkins, N. A., Copeland, N. G., W elgus, H. G., Senior, R. M., and Ley, T. J. (1992) J. Biol. Chem. 267, 4664-4671). We now report that there is a human orthologue of murine macrophage metalloelastase that we call human macrophage metalloelasta se (HME). The full-length HME cDNA spans 1.8 kilobases and contains an open reading frame of 1410 base pairs; the predicted molecular mass o f the HME proenzyme is 54 kDa. HME mRNA and protein were detected in h uman alveolar macrophages. Similar to murine macrophage metalloelastas e, HME readily undergoes NH2- and COOH-terminal processing to a mature 22-kDa form. Both recombinant HME expressed in Escherichia coli and n ative HME derived from human alveolar macrophage-conditioned media deg raded insoluble elastin. HME is a unique human metalloproteinase that possesses elastolytic activity and is expressed in alveolar macrophage s; it is therefore a candidate molecule for the causation of diseases characterized by damage to the extracellular matrix.