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. (C) 1998 Elsevier Science B.V.