title: Matrix metalloproteinase-19 is expressed in myeloid cells in an adhesion-dependent manner and associates with the cell surface.
abstract: We have previously reported the isolation of the human matrix metalloproteinase (MMP)-19 (also referred to as RASI) from a synovium of a patient suffering from rheumatoid arthritis and its expression at the cell surface of activated PBMC. In this study, we have analyzed the regulation and cell surface expression of human MMP-19 in several human cell lines and blood-derived cells. Among the cell lines analyzed, MMP-19 is largely expressed by lung fibroblasts as well as by myeloid cell lines THP-1 and HL-60. After fractionating PBMC into CD14- and CD14+ populations we found that only the latter one expresses MMP-19. Although the myeloid cell lines as well as CD14+ cells express MMP-19 without stimulation, its production can be up-regulated by phorbol esters (PMA) or by adhesion. The adhesion-dependent expression was down-regulated or even abrogated by blockade of adhesion or interfering with adhesion-controlling signaling using alpha-tocopherol. We have shown that MMP-19 associates with the cell surface of myeloid cells. This cell surface association was not affected by phospholipase C. However, acidic treatment of the THP-1-derived cell membranes abolished the immunoprecipitation of MMP-19 thereof. Moreover, a high salt treatment of THP-1 cells diminished the MMP-19 detection on the cell surface. This implicates a noncovalent attachment of MMP-19 to the cell surface. Because a truncated form of the MMP-19, in which the hemopexin-like domain was deleted (Delta(hp)MMP-19), does not associate with the surface, the hemopexin-like domain appears to be critical for the cell surface attachment of human MMP-19.
authors.affiliation: Department of Immunology, University of Konstanz, Konstanz, Germany.
authors.forename: Simon
authors.initials: S
authors.lastname: Mauch
authors.forename: Cornelia
authors.initials: C
authors.lastname: Kolb
authors.forename: Birgit
authors.initials: B
authors.lastname: Kolb
authors.forename: Thorsten
authors.initials: T
authors.lastname: Sadowski
authors.forename: Radislav
authors.initials: R
authors.lastname: Sedlacek
mesh_terms: D000595:Amino Acid Sequence; D002448:Cell Adhesion / Q000235:genetics / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics; D002458:Cell Fractionation; D002460:Cell Line; D002462:Cell Membrane / Q000201:enzymology / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic; D018922:HL-60 Cells; D006367:HeLa Cells; D006466:Hemopexin / Q000378:metabolism / Q000502:physiology; D006801:Humans; D019169:Jurkat Cells; D007963:Leukocytes, Mononuclear / Q000201:enzymology; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis; D053505:Matrix Metalloproteinases, Secreted; D008666:Metalloendopeptidases / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D008969:Molecular Sequence Data; D022423:Myeloid Cells / Q000166:cytology / Q000201:enzymology* / Q000502:physiology; D015854:Up-Regulation / Q000235:genetics
chemical_list: D018950:Lipopolysaccharide Receptors; D006466:Hemopexin; D053505:Matrix Metalloproteinases, Secreted; D008666:Metalloendopeptidases; C108362:matrix metalloproteinase 19