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(American Journal of Pathology. 2002;161:1749-1759.)
© 2002 American Society for Investigative Pathology

Guanylate-Binding Protein-1 Expression Is Selectively Induced by Inflammatory Cytokines and Is an Activation Marker of Endothelial Cells during Inflammatory Diseases

Clara Lubeseder-Martellato^*, Eric Guenzi^*, Anita Jörg^*, Kristin Töpolt^*, Elisabeth Naschberger^*, Elisabeth Kremmer, Christian Zietz, Erwin Tschachler, Peter Hutzler^¶, Martin Schwemmle^||, Kathrin Matzen^*, Thomas Grimm^*, Barbara Ensoli^** and Michael Stürzl^*

From the Department of Virus-Induced Vasculopathy,^* Institute of Molecular Virology, and the Department of Pathology,^¶ GSF-National Research Center for Environment and Health, Neuherberg, Germany; the Institute of Molecular Immunology, GSF-National Research Center for Environment and Health, Munich, Germany; the Institute of Pathology, Ludwig Maximilians University, Munich, Germany; the Department of Virology,^|| Institute of Medical Microbiology and Hygiene, University of Freiburg, Freiburg, Germany; the Department of Dermatology, Division of Immunology, Allergy, and Infectious Diseases, University of Vienna Medical School, Vienna, Austria; and the Laboratory of Virology,^** Retrovirus Division, Istituto Superiore di Sanità, Rome, Italy

During angiogenesis and inflammatory processes, endothelial cells acquire different activation phenotypes, whose identification may help in understanding the complex network of angiogenic and inflammatory interactions in vivo. To this goal we investigated the expression of the human guanylate-binding protein (GBP)-1 that is highly induced by inflammatory cytokines (ICs) and, therefore, may characterize IC-activated cells. Using a new rat monoclonal antibody raised against GBP-1, we show that GBP-1 is a cytoplasmic protein and that its expression in endothelial cells is selectively induced by interferon-, interleukin-1, interleukin-1ß, or tumor necrosis factor-, but not by other cytokines, chemokines, or growth factors. Moreover, we found that GBP-1 expression is highly associated with vascular endothelial cells as confirmed by the simultaneous detection of GBP-1 and the endothelial cell-associated marker CD31 in a broad range of human tissues. Notably, GBP-1 expression was undetectable in the skin, but it was highly induced in vessels of skin diseases with a high-inflammatory component including psoriasis, adverse drug reactions, and Kaposi’s sarcoma. These results indicate that GBP-1 is a novel cellular activation marker that characterizes the IC-activated phenotype of endothelial cells.

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