Abstract
Monocyte/macrophages play important roles in regulating tissue growth and angiogenesis through the controlled release of heparin-binding growth factors such as fibroblast growth factor (FGF), vascular endothelial growth factor, 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 interactions with their signal-transducing receptors on target cells. Here we report on the nature of HSPGs inducibly expressed on the surface of macrophages that confer these cells with the capacity to regulate endogenous growth factor activity. We reveal that activated human macrophages express only a single major 48-kDa cell surface HSPG, syndecan-2 (fibroglycan) as the result of de novo RNA and protein synthesis. In addition, we demonstrate this macrophage HSPG selectively binds the macrophage-derived growth factors FGF-2, vascular endothelial growth factor and heparin binding EGF and can present FGF-2 in a form that transactivates receptor-bearing BaF32 cells. These results 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 target cells in vivo.
Highlights
Mononuclear phagocytes are recruited from peripheral blood to the sites of tissue injury during the normal physiological processes of wound healing and inflammation as well as in pathological processes such as atherogenesis and tumor development where they play a key role in stimulating new tissue growth [1, 2]
Immunochemical Detection of Heparan Sulfate at the Surface of Differentiated Human Macrophages—To measure cell surface heparan sulfate proteoglycans (HSPGs) expression in primary human monocyte/macrophages, we exploited the specificity of the monoclonal antibody 3G10 to detect unsaturated ⌬4,5 glucuronyl residues in core HS chains generated by prior treatment of intact cells with the enzyme heparan sulfate lyase
We first questioned whether mobilization of HS to the cell surface is triggered by differentiation of blood monocytes to MDMs or by exposure to proinflammatory mediators that activate macrophages and induce synthesis of heparin-binding growth factors
Summary
Mononuclear phagocytes are recruited from peripheral blood to the sites of tissue injury during the normal physiological processes of wound healing and inflammation as well as in pathological processes such as atherogenesis and tumor development where they play a key role in stimulating new tissue growth [1, 2]. We report on the nature of HSPGs inducibly expressed on the surface of macrophages that confer these cells with the capacity to regulate endogenous growth factor activity.
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