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 recently 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., Welgus, 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 metalloelastase (HME). The full-length HME cDNA spans 1.8 kilobases and contains an open reading frame of 1410 base pairs; the predicted molecular mass of the HME proenzyme is 54 kDa. HME mRNA and protein were detected in human alveolar macrophages. Similar to murine macrophage metalloelastase, HME readily undergoes NH2- and COOH-terminal processing to a mature 22-kDa form. Both recombinant HME expressed in Escherichia coli and native HME derived from human alveolar macrophage-conditioned media degraded insoluble elastin. HME is a unique human metalloproteinase that possesses elastolytic activity and is expressed in alveolar macrophages; it is therefore a candidate molecule for the causation of diseases characterized by damage to the extracellular matrix.
Shapiro
S D
SD
Department of Medicine, Jewish Hospital, Washington University Medical Center, St. Louis, Missouri 63110.
Kobayashi
D K
DK
Ley
T J
TJ
D000595:Amino Acid Sequence; D001483:Base Sequence; D002478:Cells, Cultured; D003001:Cloning, Molecular; D018076:DNA, Complementary; D004549:Elastin / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D016676:Macrophages, Alveolar / Q000201:enzymology*; D053508:Matrix Metalloproteinase 12; D008666:Metalloendopeptidases / Q000235:genetics*; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
D018076:DNA, Complementary; D012333:RNA, Messenger; D004549:Elastin; D008666:Metalloendopeptidases; C507122:MMP12 protein, human; D053508:Matrix Metalloproteinase 12