Inducible expression of the cell surface heparan sulfate proteoglycan syndecan-2 (fibroglycan) on human activated macrophages can regulate fibroblast growth factor action.
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.
Clasper
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S
University of Oxford, Molecular Immunology Group, Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DU United Kingdom.
Vekemans
S
S
Fiore
M
M
Plebanski
M
M
Wordsworth
P
P
David
G
G
Jackson
D G
DG
D043925:Angiogenesis Inducing Agents / Q000502:physiology; D002460:Cell Line; D005346:Fibroblast Growth Factors / Q000502:physiology*; D006493:Heparin / Q000378:metabolism; D006801:Humans; D008262:Macrophage Activation; D008264:Macrophages / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D011509:Proteoglycans / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology; D051496:Receptor, Fibroblast Growth Factor, Type 1; D017468:Receptors, Fibroblast Growth Factor / Q000502:physiology; D053669:Syndecan-2
D043925:Angiogenesis Inducing Agents; D008562:Membrane Glycoproteins; D011509:Proteoglycans; D012333:RNA, Messenger; D017468:Receptors, Fibroblast Growth Factor; C508245:SDC2 protein, human; D053669:Syndecan-2; D005346:Fibroblast Growth Factors; D006493:Heparin; C496348:FGFR1 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1