REGULATION OF MONOCYTE CD36 AND THROMBOSPONDIN-1 EXPRESSION BY SOLUBLE MEDIATORS

CD36 is an 88-kD integral membrane protein expressed on platelets, mon ocytes, macrophages, certain microvascular endothelia, and retinal pig ment epithelium. It functions as an adhesive receptor for thrombospond in-1 (TSP-1), collagen, and malaria-infected erythrocytes and as a sca venger receptor for oxidized LDL and photoreceptor outer segments. The CD36-TSP-1 interaction plays a role in cell adhesion and the phagocyt osis of apoptotic cells by macrophages. Because of the potential impor tance of the CD36-TSP-1 interaction in mediating atherogenic and infla mmatory processes, we studied their expression in human peripheral blo od monocytes exposed to soluble mediators known to regulate inflammati on and atherogenesis. RNase protection assays showed 6- to 12-fold inc reases in CD36 mRNA in response to interleukin-4, monocyte colony-stim ulating factor, and phorbol myristate acetate, while lipopolysaccharid e and dexamethasone strongly downregulated CD36 mRNA. The downregulati on of CD36 mRNA was associated with the disappearance of surface expre ssion of CD36 antigen and loss of TSP-1 surface-binding capacity. Upre gulation 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-stimulatin g factor showed a rapid increase in TSP-1 mRNA expression. Moreover, w hile 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 ef fect on CD36 mRNA, rapidly increased steady-state TSP-1 mRNA. Thus, ex pression of both CD36 and its ligand TSP-1 is regulated by soluble med iators, although certain mediators induce concordant changes and other s discordant changes.