Macrophage and foam cell release of matrix-bound growth factors. Role of plasminogen activation
Journal of Biological Chemistry
We have determined whether macrophage derived-foam cells, a prominent component of the atherosclerotic lesion, express more urokinase-type plasminogen activator (uPA) and whether their ability to generate plasmin stimulates the release of matrix-bound growth factors. Steady state levels of uPA mRNA and both membrane and intracellular uPA activities were significantly increased in foam cells. When cultured on cell-derived matrices containing bound 125I-basic fibroblast growth factor (bFGF), both macrophage and foam cells released intact 125I-bFGF into their media. The release of 125I-bFGF by either cell was significantly enhanced in the presence of plasminogen. However, foam cells, which expressed more membrane uPA, released more 125I-bFGF than control cells. The release of matrix- bound bFGF was independent of heparanase activity, since neither macrophage nor foam cells degraded 35SO4-labeled heparan sulfate proteoglycans. In addition, media derived from foam cells cultured on cell-derived matrices in the presence of plasminogen had increased levels of transforming growth factor (TGF) β activity as compared to cells grown in the absence of plasminogen. In contrast, plasminogen had no effect on TGF-β activity recovered in the media of foam cells grown on plastic. Moreover, when macrophage were cultured on matrices containing bound 125I-TGF-β, the release of labeled TGF-β was increased in the presence of plasminogen. This is the first demonstration that foam cells can release two important growth regulators, bFGF and TGF-β, from the extracellular matrix, and provides a mechanism by which macrophage and foam cells can stimulate atherosclerotic lesion development.
Falcone, D., McCaffrey, T., Haimovitz-Friedman, A., Vergilio -, J., & Nicholson, A. (1993). Macrophage and foam cell release of matrix-bound growth factors. Role of plasminogen activation. Journal of Biological Chemistry, 268 (16). Retrieved from https://hsrc.himmelfarb.gwu.edu/smhs_medicine_facpubs/4890