EXPRESSION OF PLATELET-DERIVED GROWTH-FACTOR-BETA RECEPTOR ON HUMAN MONOCYTE-DERIVED MACROPHAGES AND EFFECTS OF PLATELET-DERIVED GROWTH-FACTOR BB DIMER ON THE CELLULAR FUNCTION

Platelet-derived growth factor (PDGF) plays an important role in the p rocess of atherosclerosis which is characterized by the presence of ma crophage-derived foam cells. In the present study, the induction of th e mRNA of PDGF-beta receptor was demonstrated during cell differentiat ion of human monocyte-macrophages, whereas no mRNA was detected in the cells during the early days of culture. Flow cytometry analysis using antibodies specific for PDGF-beta receptor and CD14 showed the presen ce of both PDGF-beta receptor and CD14 on human monocyte-derived macro phages, whereas no PDGF-beta receptor was detected on human monocytes 4 h after cell adhesion to a culture dish. In the binding assay of PDG F-BB on human monocyte-derived macrophages, a saturable and high affin ity binding site with K(d) of 27.5 pM and B(max) of 23.3 fmol/mg of ce ll protein was demonstrated. When human monocytes were cultured in the presence of the protein kinase C inhibitor staurosporine, PDGF-beta r eceptor induction was inhibited, and tetradecanoylphorbol acetate enha nced PDGF-beta receptor expression in human monocyte-derived macrophag es, indicating that PDGF-beta receptor expression is associated with m aturation and differentiation of monocyte-macrophages through the acti vation of protein kinase C. In response to PDGF-BB homodimer, PDGF-bet a receptor was phosphorylated, and thymidine uptake and inositol trisp hosphate production were stimulated in monocyte-derived macrophages. F urthermore, PDGF-BB suppressed the production of macrophage colony-sti mulating factor in macrophages. The expression of PDGF-beta receptor o n human monocyte-derived macrophages suggests that PDGF influences the process of atherosclerosis by regulating the function of macrophages as well as smooth muscle cells in the vascular wall.