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 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.
Inaba
T
T
Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Shimano
H
H
Gotoda
T
T
Harada
K
K
Shimada
M
M
Ohsuga
J
J
Watanabe
Y
Y
Kawamura
M
M
Yazaki
Y
Y
Yamada
N
N
D000818:Animals; D001665:Binding Sites; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000166:cytology / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D017479:Receptors, Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism*
D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D016173:Macrophage Colony-Stimulating Factor; D002784:Cholesterol; D017479:Receptors, Platelet-Derived Growth Factor