Regulation of Plasminogen Receptor Expression on Monocytoid Cells by β1-Integrin-dependent Cellular Adherence to Extracellular Matrix Proteins

Abstract

Plasminogen binding sites function to arm cell surfaces with the proteolytic activity of plasmin, critical for degradation of extracellular matrices. We have assessed the effects of adhesion of the representative monocytoid cell lines, THP-1 and U937, to purified extracellular matrix proteins on their expression of plasminogen receptors. After adhesion to immobilized fibronectin, adherent and nonadherent subpopulations of cells were separated. Plasminogen binding to the nonadherent population of cells increased 3-fold, whereas binding to the adherent population decreased by 60%. These changes were due to differences in the plasminogen binding capacities of the cells, while the affinities of the cells for plasminogen were unchanged. The up-regulation of receptor expression in the nonadherent cell population was: 1) induced rapidly and reversibly, 2) independent of new protein synthesis, 3) required an interaction between adherent and nonadherent cell populations, and 4) associated with an enhanced ability of the cells to promote plasminogen activation and to degrade fibronectin. Other immobilized adhesive proteins, laminin and vitronectin, also supported up-regulation of plasminogen receptors in the nonadherent cells. Carboxypeptidase B treatment eliminated the increment in the plasminogen binding capacity of the nonadherent cells, suggesting that the increase in binding was due to exposure of new carboxyl-terminal lysyl residues on the cell surfaces. Furthermore, both the adherence of the cells and up-regulation of plasminogen binding sites was abolished by beta1-integrin monoclonal antibodies. These results suggest that proteins found in extracellular matrices have the capacity to modulate the expression of plasminogen binding sites, thus regulating local proteolysis and cell migration.

Regulation of plasminogen binding to neutrophils

“…63 Therefore, the enhanced plasminogen binding induced by PMA may also be a reflection of remodeling of the cell membrane. In previous studies, 20,23 we showed that adhesion and de-adhesion of cells influence the expression of plasminogenbinding sites, which may also be an extension of this concept.…”

“…20 Adhesion of such cells to matrix proteins down-regulates the plasminogen-binding capacity of the adherent cells and upregulates it in the nonadherent cells. 20,23 Furthermore, Felez et al 20,24 reported that short-term (overnight) culturing of neutrophils or monocytes leads to a marked increase in the number of plasminogen-binding sites expressed by these cells. Such modulation of plasminogen-binding capacity may be particularly relevant to neutrophil recruitment as early participants in the inflammatory response.…”

Plasminogen binding and activation at the breast cancer cell surface: the integral role of urokinase activity

“…Additionally, carboxypeptidase treatment to remove C-terminal lysine residues from proteins has been shown to cause marked decreases in plg binding in a number of cell types [20,22,55]. In our experience, however, pre-treatment with high concentrations of pln at 37°C devastates cell viability in vitro .…”

L-Type Calcium Channel Blockers Exert an Antiinflammatory Effect by Suppressing Expression of Plasminogen Receptors on Macrophages

“…Human monocytoid THP-1 cells were stimulated to differentiate with 250 U/ml IFNγ (eBioscience) + 100 nmol/L VD3 (Calbiochem) for 0-2 days in complete growth medium under conditions similar to those described by Kim et al12.…”