The matrix metalloprotease matrilysin (PUMP) is expressed in developing human mononuclear phagocytes.
Matrilysin (PUMP, MMP-7) is a member of the metalloprotease gene family, whose constituents are responsible for the remodeling of extracellular matrix. The matrilysin protein is a 28-kDa zymogen possessing catalytic activities against a broad range of extracellular matrix substrates including proteoglycans, gelatin, fibronectin, laminin, and elastin. To gain insights into the biological expression of matrilysin in human cell types, we generated a monospecific, polyclonal antibody against a 16-amino acid sequence derived from its catalytic domain, a region which lacked significant homology with other matrix metalloenzymes. We found this antibody capable of precipitating a 28-kDa protein from the conditioned media of human bone marrow-derived promonocytes and human peripheral blood monocytes cultivated in vitro. Promonocyte matrilysin was rapidly converted to a 19-kDa form by organomercurial activation. While matrilysin was constitutively synthesized by bone marrow-derived promonocytes, its secretion was markedly up-regulated by the mononuclear phagocyte activator, lipopolysaccharide. Furthermore, despite its expression in monocyte precursors, blood monocytes, and monocyte-derived macrophages, matrilysin was not synthesized by human alveolar macrophages under any tested condition. In situ hybridization studies with matrilysin cRNA confirmed the presence of specific mRNA in both human promonocytes and monocytes. Moreover, a marked increase in hybridizable mRNA was observed with lipopolysaccharide treatment suggesting that matrilysin synthesis is pretranslationally regulated. In summary, this represents the first report documenting constitutive and regulated synthesis of matrilysin by a normal human cell type and suggests that matrilysin is expressed as a significant secreted product of mononuclear phagocytes at an intermediate stage of cellular differentiation.
Busiek
D F
DF
Division of Hematology/Oncology, Jewish Hospital, Washington University Medical Center, St. Louis, Missouri 63110.
Ross
F P
FP
McDonnell
S
S
Murphy
G
G
Matrisian
L M
LM
Welgus
H G
HG
D000595:Amino Acid Sequence; D001853:Bone Marrow / Q000201:enzymology; D001854:Bone Marrow Cells; D002454:Cell Differentiation; D002478:Cells, Cultured; D006801:Humans; D016676:Macrophages, Alveolar / Q000201:enzymology; D020783:Matrix Metalloproteinase 7; D008666:Metalloendopeptidases / Q000096:biosynthesis* / Q000235:genetics; D008969:Molecular Sequence Data; D005810:Multigene Family; D009693:Nucleic Acid Hybridization; D010586:Phagocytes / Q000187:drug effects / Q000201:enzymology*; D012313:RNA / Q000235:genetics; D018075:RNA, Complementary; D012333:RNA, Messenger / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid
D018075:RNA, Complementary; D012333:RNA, Messenger; D012313:RNA; D008666:Metalloendopeptidases; D020783:Matrix Metalloproteinase 7