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

• Published in: The Journal of biological chemistry Vol. 268; no. 32; pp. 24353 - 24360
• Main Authors: INABA, T, SHIMANO, H, GOTODA, T, HARADA, K, SHIMADA, M, OHSUGA, J.-I, WATANABE, Y, KAWAMURA, M, YAZAKI, Y, YAMADA, N
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Biochemistry and Molecular Biology 15-11-1993
• Subjects: Animals; Binding Sites; Biological and medical sciences; Cell receptors; Cell structures and functions; Cells, Cultured; Cholesterol - metabolism; Fundamental and applied biological sciences. Psychology; Hormone receptors. Growth factor receptors. Cytokine receptors. Prostaglandin receptors; Humans; Macrophage Colony-Stimulating Factor - biosynthesis; Mice; Mice, Inbred C57BL; Molecular and cellular biology; Monocytes - cytology; Monocytes - metabolism; Platelet-Derived Growth Factor - metabolism; Receptors, Platelet-Derived Growth Factor - genetics; Receptors, Platelet-Derived Growth Factor - metabolism; RNA, Messenger - metabolism; Human; Membrane receptor; Atherosclerosis; Cell differentiation; Gene expression; Platelet derived growth factor; Growth factor; Macrophage
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(20)80533-X

Platelet-derived growth factor (PDGF) plays an important role in the process of atherosclerosis which is characterized by
the presence of macrophage-derived foam cells. In the present study, the induction of the mRNA of PDGF-beta receptor was demonstrated
during cell differentiation 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 presence of both
PDGF-beta receptor and CD14 on human monocyte-derived macrophages, whereas no PDGF-beta receptor was detected on human monocytes
4 h after cell adhesion to a culture dish. In the binding assay of PDGF-BB on human monocyte-derived macrophages, a saturable
and high affinity binding site with Kd of 27.5 pM and Bmax of 23.3 fmol/mg of cell protein was demonstrated. When human monocytes
were cultured in the presence of the protein kinase C inhibitor staurosporine, PDGF-beta receptor induction was inhibited,
and tetradecanoylphorbol acetate enhanced PDGF-beta receptor expression in human monocyte-derived macrophages, indicating
that PDGF-beta receptor expression is associated with maturation and differentiation of monocyte-macrophages through the activation
of protein kinase C. In response to PDGF-BB homodimer, PDGF-beta receptor was phosphorylated, and thymidine uptake and inositol
trisphosphate production were stimulated in monocyte-derived macrophages. Furthermore, PDGF-BB suppressed the production of
macrophages colony-stimulating factor in macrophages. The expression of PDGF-beta receptor on 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.