Human guanylate binding protein-1 (hGBP-1) characterizes and establishes a non-angiogenic endothelial cell activation phenotype in inflammatory diseases.
Blood vessel activation in inflammatory diseases is triggered by a myriad of different factors that partially reveal opposite activities on endothelial cells (EC). For example, inflammatory cytokines (IC) inhibit EC proliferation and induce cell adhesiveness for leukocytes. In contrast, angiogenic growth factors (AGF) activate EC proliferation and inhibit cell adhesiveness for leukocytes. In consequence, IC and AGF may induce two different activation phenotypes in EC that appear in a temporally and/or spatially coordinated manner in inflammatory tissues. Human guanylate binding protein-1 (hGBP-1) is a member of the large GTPase protein family. New results demonstrate that hGBP-1 is a specific marker of IC-activated EC that allows to differentiate the IC- and AGF-activated phenotype of EC at the single cell level, both in vitro and in vivo. In addition, hGBP-1 is the key mediator of the inhibitory effects of IC on EC proliferation and invasiveness. Both the expression pattern of hGBP-1 and its activity in EC supported the hypothesis that IC- and AGF-activation induce distinct adversely related phenotypes in EC. In future, hGBP-1 may be used as a marker to monitor the IC-induced phenotype of EC in inflammation and may also be exploited as a target to modulate EC activity in inflammatory diseases and tumor angiogenesis.
Naschberger
Elisabeth
E
Division of Molecular and Experimental Surgery, Department of Surgery, University of Erlangen-Nürnberg, Schwabachanlage 10, 91054 Erlangen, Germany.
Bauer
Michael
M
Stürzl
Michael
M
D020533:Angiogenesis Inhibitors / Q000502:physiology; D015536:Down-Regulation; D004730:Endothelium, Vascular / Q000166:cytology / Q000503:physiopathology*; D019204:GTP-Binding Proteins / Q000096:biosynthesis / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000503:physiopathology*; D016898:Interferon-alpha / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis; D010641:Phenotype
D020533:Angiogenesis Inhibitors; C490287:GBP1 protein, human; D016898:Interferon-alpha; D007371:Interferon-gamma; D020781:Matrix Metalloproteinase 1; D019204:GTP-Binding Proteins