Regulation of monocyte CD36 and thrombospondin-1 expression by soluble mediators.
CD36 is an 88-kD integral membrane protein expressed on platelets, monocytes, macrophages, certain microvascular endothelia, and retinal pigment epithelium. It functions as an adhesive receptor for thrombospondin-1 (TSP-1), collagen, and malaria-infected erythrocytes and as a scavenger receptor for oxidized LDL and photoreceptor outer segments. The CD36-TSP-1 interaction plays a role in cell adhesion and the phagocytosis of apoptotic cells by macrophages. Because of the potential importance of the CD36-TSP-1 interaction in mediating atherogenic and inflammatory processes, we studied their expression in human peripheral blood monocytes exposed to soluble mediators known to regulate inflammation and atherogenesis. RNase protection assays showed 6- to 12-fold increases in CD36 mRNA in response to interleukin-4, monocyte colony-stimulating factor, and phorbol myristate acetate, while lipopolysaccharide and dexamethasone strongly downregulated CD36 mRNA. The downregulation of CD36 mRNA was associated with the disappearance of surface expression of CD36 antigen and loss of TSP-1 surface-binding capacity. Upregulation of CD36 mRNA was associated with a modest increase in surface antigen expression and a larger expansion of an intracellular pool of CD36. As with CD36, monocytes treated with monocyte colony-stimulating factor showed a rapid increase in TSP-1 mRNA expression. Moreover, while dexamethasone treatment decreased CD36 expression, it resulted in a rapid increase in TSP-1 mRNA, and while PMA increased CD36 mRNA, it rapidly decreased TSP-1 expression. Interferon gamma, which had no effect on CD36 mRNA, rapidly increased steady-state TSP-1 mRNA. Thus, expression of both CD36 and its ligand TSP-1 is regulated by soluble mediators, although certain mediators induce concordant changes and others discordant changes.
Yesner
L M
LM
Department of Medicine (Hematology-Oncology), Cornell University Medical College, New York, NY 10021, USA.
Huh
H Y
HY
Pearce
S F
SF
Silverstein
R L
RL
D018955:CD36 Antigens / Q000096:biosynthesis* / Q000235:genetics; D003907:Dexamethasone / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012995:Solubility; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D019699:Thrombospondins
D018955:CD36 Antigens; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D019699:Thrombospondins; D015847:Interleukin-4; D003907:Dexamethasone; D016173:Macrophage Colony-Stimulating Factor; D013755:Tetradecanoylphorbol Acetate