Human monocyte-endothelial cell interaction induces platelet-derived growth factor expression.

OBJECTIVE

The purpose of this study was to investigate whether the synthesis of platelet-derived growth factor (PDGF), a major mitogen and chemoattractant for vascular smooth muscle cells, was induced by the direct cell-to-cell interaction between human monocytes and umbilical vein endothelial cells (ECs).

METHODS

PDGF protein and mRNA expression were determined by cellular ELISA, immunohistochemical and Northern blot analyses.

RESULTS

Coculture of monocytes and ECs secreted a large amount of PDGF into the supernatant, whereas culture of ECs or monocytes alone induced low levels of PDGF production. In Northern blot analysis, substantial amounts of PDGF-A and -B mRNA were induced by coculture of monocytes with ECs. Immunohistochemistry revealed that PDGF-B chain protein was detectable in both ECs and monocytes. PDGF production by ECs induced by conditioned medium of the coculture was significantly inhibited by Abs against interleukin-1 beta (IL-1 beta) and tumor necrosis factor- alpha (TNF alpha).

CONCLUSIONS

These results indicate that the direct cell-to-cell interaction between human monocytes and ECs induces PDGF synthesis in both types of cells, suggesting that PDGF produced locally by monocyte-EC adhesive interaction plays an important role in the pathogenesis of atherosclerosis by promoting the migration and accumulation of vascular smooth muscle cells.