HUMAN MONOCYTE-ENDOTHELIAL CELL-INTERACTION INDUCES PLATELET-DERIVED GROWTH-FACTOR EXPRESSION

Objective: The purpose of this study was to investigate whether the sy nthesis of platelet-derived growth factor (PDGF), a major mitogen and chemoattractant for vascular smooth muscle cells, was induced by the d irect cell-to-cell interaction between human monocytes and umbilical v ein endothelial cells (ECs). Methods: PDGF protein and mRNA expression were determined by cellular ELISA, immunohistochemical and Northern b lot analyses. Results: Coculture of monocytes and ECs secreted a large amount of PDGF into the supernatant, whereas culture of ECs or monocy tes alone induced low levels of PDGF production. In Northern blot anal ysis, substantial amounts of PDGF-A and -B mRNA were induced by cocult ure of monocytes with ECs. Immunohistochemistry revealed that PDGF-B c hain protein was detectable in both ECs and monocytes. PDGF production by ECs induced by conditioned medium of the coculture was significant ly inhibited by Abs against interleukin-1 beta (IL-1 beta) and tumor n ecrosis factor-alpha (TNF alpha). Conclusions: These results indicate that the direct cell-to-cell interaction between human monocytes and E Cs induces PDGF synthesis in both types of cells, suggesting that PDGF produced locally by monocyte-EC adhesive interaction plays an importa nt role in the pathogenesis of atherosclerosis by promoting the migrat ion and accumulation of vascular smooth muscle cells. (C) 1998 Elsevie r Science B.V.