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Published on: March 8, 2017
Matrix metalloproteinase-19 is expressed in myeloid cells in an adhesion-dependent manner and associates with the
Simon Mauch1, Cornelia Kolb, Birgit Kolb
1Department of Immunology, University of Konstanz, Konstanz, Germany.
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.
Insights
Human matrix metalloproteinase-19 (MMP-19) is expressed on myeloid cells and lung fibroblasts. Its cell surface attachment is noncovalent, mediated by the hemopexin-like domain, and can be regulated by adhesion.
Area of Science:
- Biochemistry
- Cell Biology
- Immunology
Background:
- Human matrix metalloproteinase-19 (MMP-19), also known as RASI, was previously isolated from rheumatoid arthritis synovium.
- MMP-19 is expressed on the cell surface of activated peripheral blood mononuclear cells (PBMCs).
Purpose of the Study:
- To analyze the regulation and cell surface expression of human MMP-19 in various human cell lines and blood cells.
- To elucidate the mechanism of MMP-19 cell surface association.
Main Methods:
- Analysis of MMP-19 expression in lung fibroblasts and myeloid cell lines (THP-1, HL-60).
- Fractionation of PBMCs into CD14- and CD14+ populations.
- Up-regulation studies using phorbol esters (PMA) and adhesion.
- Investigation of cell surface association using phospholipase C, acidic treatment, high salt treatment, and a truncated MMP-19 mutant.
Main Results:
- MMP-19 is predominantly expressed in lung fibroblasts and myeloid cell lines THP-1 and HL-60.
- CD14+ PBMCs express MMP-19, with production up-regulated by PMA or adhesion.
- Adhesion-dependent expression is modulated by alpha-tocopherol.
- MMP-19 associates noncovalently with the cell surface via its hemopexin-like domain.
Conclusions:
- Human MMP-19 is expressed on lung fibroblasts and myeloid cells, particularly CD14+ PBMCs.
- Cell surface association of MMP-19 is mediated by its hemopexin-like domain through noncovalent interactions.
- MMP-19 expression and adhesion-dependent regulation offer potential therapeutic targets.
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