Inducible expression of the cell surface heparan sulfate proteoglycan syndecan-2 (fibroglycan) on human activated macrophages can regulate fibroblastgrowth factor action

Monocyte/macrophages play important roles in regulating tissue growth and a ngiogenesis through the controlled release of heparin-binding growth factor s such as fibroblast growth factor (FGF), vascular endothelial growth facto r, and heparin binding epidermal growth factor. The action of these potent growth mediators is known to be regulated by adsorption to heparan sulfate proteoglycans (HSPGs) on the surface and within the extracellular matrix of other neighboring cells, which respectively promote or restrict interactio ns with their signal-transducing receptors on target cells. Here we report on the nature of HSPGs inducibly expressed on the surface of macrophages th at confer these cells with the capacity to regulate endogenous growth facto r activity. We reveal that activated human macrophages express only a singl e major 48-kDa cell surface HSPG, syndecan-2 (fibroglycan) as the result of de novo RNA and protein synthesis. In addition, we demonstrate this macrop hage HSPG selectively binds the macrophage-derived growth factors FGF-8, va scular endothelial growth factor and heparin binding ECF and can present FG F-8 in a form that transactivates receptor-bearing BaF32 cells. These resul ts define a novel and unique proteoglycan profile for macrophages and imply a key role for syndecan-2 in the delivery of sequestered growth factors by inflammatory macrophages for productive binding to their appropriate targe t cells ire vivo.