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Review ArticleReview

Different Faces of the Heme-Heme Oxygenase System in Inflammation

Frank A. D. T. G. Wagener, Hans-Dieter Volk, Dean Willis, Nader G. Abraham, Miguel P. Soares, Gosse J. Adema and Carl G. Figdor
Pharmacological Reviews September 2003, 55 (3) 551-571; DOI: https://doi.org/10.1124/pr.55.3.5
Frank A. D. T. G. Wagener
Department of Tumor Immunology, University Medical Center Nijmegen, Nijmegen, The Netherlands (F.A.D.T.G.W., G.J.A., C.G.F.); Department of Medical Immunology, Charité, Humboldt University, Berlin, Germany (H.-D.V.); Department of Pharmacology, University College, London, England (D.W.); Department of Pharmacology, New York Medical College, Valhalla, New York (N.G.A.); Beth Israel Deaconess Medical Center, Department of Surgery, Harvard Medical School, Boston, Massachusetts (M.P.S.); and Inflammation Laboratory, Institute Gulbenkian for Science, Lisbon, Portugal (M.P.S.)
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Hans-Dieter Volk
Department of Tumor Immunology, University Medical Center Nijmegen, Nijmegen, The Netherlands (F.A.D.T.G.W., G.J.A., C.G.F.); Department of Medical Immunology, Charité, Humboldt University, Berlin, Germany (H.-D.V.); Department of Pharmacology, University College, London, England (D.W.); Department of Pharmacology, New York Medical College, Valhalla, New York (N.G.A.); Beth Israel Deaconess Medical Center, Department of Surgery, Harvard Medical School, Boston, Massachusetts (M.P.S.); and Inflammation Laboratory, Institute Gulbenkian for Science, Lisbon, Portugal (M.P.S.)
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Dean Willis
Department of Tumor Immunology, University Medical Center Nijmegen, Nijmegen, The Netherlands (F.A.D.T.G.W., G.J.A., C.G.F.); Department of Medical Immunology, Charité, Humboldt University, Berlin, Germany (H.-D.V.); Department of Pharmacology, University College, London, England (D.W.); Department of Pharmacology, New York Medical College, Valhalla, New York (N.G.A.); Beth Israel Deaconess Medical Center, Department of Surgery, Harvard Medical School, Boston, Massachusetts (M.P.S.); and Inflammation Laboratory, Institute Gulbenkian for Science, Lisbon, Portugal (M.P.S.)
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Nader G. Abraham
Department of Tumor Immunology, University Medical Center Nijmegen, Nijmegen, The Netherlands (F.A.D.T.G.W., G.J.A., C.G.F.); Department of Medical Immunology, Charité, Humboldt University, Berlin, Germany (H.-D.V.); Department of Pharmacology, University College, London, England (D.W.); Department of Pharmacology, New York Medical College, Valhalla, New York (N.G.A.); Beth Israel Deaconess Medical Center, Department of Surgery, Harvard Medical School, Boston, Massachusetts (M.P.S.); and Inflammation Laboratory, Institute Gulbenkian for Science, Lisbon, Portugal (M.P.S.)
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Miguel P. Soares
Department of Tumor Immunology, University Medical Center Nijmegen, Nijmegen, The Netherlands (F.A.D.T.G.W., G.J.A., C.G.F.); Department of Medical Immunology, Charité, Humboldt University, Berlin, Germany (H.-D.V.); Department of Pharmacology, University College, London, England (D.W.); Department of Pharmacology, New York Medical College, Valhalla, New York (N.G.A.); Beth Israel Deaconess Medical Center, Department of Surgery, Harvard Medical School, Boston, Massachusetts (M.P.S.); and Inflammation Laboratory, Institute Gulbenkian for Science, Lisbon, Portugal (M.P.S.)
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Gosse J. Adema
Department of Tumor Immunology, University Medical Center Nijmegen, Nijmegen, The Netherlands (F.A.D.T.G.W., G.J.A., C.G.F.); Department of Medical Immunology, Charité, Humboldt University, Berlin, Germany (H.-D.V.); Department of Pharmacology, University College, London, England (D.W.); Department of Pharmacology, New York Medical College, Valhalla, New York (N.G.A.); Beth Israel Deaconess Medical Center, Department of Surgery, Harvard Medical School, Boston, Massachusetts (M.P.S.); and Inflammation Laboratory, Institute Gulbenkian for Science, Lisbon, Portugal (M.P.S.)
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Carl G. Figdor
Department of Tumor Immunology, University Medical Center Nijmegen, Nijmegen, The Netherlands (F.A.D.T.G.W., G.J.A., C.G.F.); Department of Medical Immunology, Charité, Humboldt University, Berlin, Germany (H.-D.V.); Department of Pharmacology, University College, London, England (D.W.); Department of Pharmacology, New York Medical College, Valhalla, New York (N.G.A.); Beth Israel Deaconess Medical Center, Department of Surgery, Harvard Medical School, Boston, Massachusetts (M.P.S.); and Inflammation Laboratory, Institute Gulbenkian for Science, Lisbon, Portugal (M.P.S.)
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Abstract

The heme-heme oxygenase system has recently been recognized to possess important regulatory properties. It is tightly involved in both physiological as well as pathophysiological processes, such as cytoprotection, apoptosis, and inflammation. Heme functions as a double-edged sword. In moderate quantities and bound to protein, it forms an essential element for various biological processes, but when unleashed in large amounts, it can become toxic by mediating oxidative stress and inflammation. The effect of this free heme on the vascular system is determined by extracellular factors, such as hemoglobin/heme-binding proteins, haptoglobin, albumin, and hemopexin, and intracellular factors, including heme oxygenases and ferritin. Heme oxygenase (HO) enzyme activity results in the degradation of heme and the production of iron, carbon monoxide, and biliverdin. All these heme-degradation products are potentially toxic, but may also provide strong cytoprotection, depending on the generated amounts and the microenvironment. Pre-induction of HO activity has been demonstrated to ameliorate inflammation and mediate potent resistance to oxidative injury. A better understanding of the complex heme-heme

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Pharmacological Reviews: 55 (3)
Pharmacological Reviews
Vol. 55, Issue 3
1 Sep 2003
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Review ArticleReview

Different Faces of the Heme-Heme Oxygenase System in Inflammation

Frank A. D. T. G. Wagener, Hans-Dieter Volk, Dean Willis, Nader G. Abraham, Miguel P. Soares, Gosse J. Adema and Carl G. Figdor
Pharmacological Reviews September 1, 2003, 55 (3) 551-571; DOI: https://doi.org/10.1124/pr.55.3.5

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Review ArticleReview

Different Faces of the Heme-Heme Oxygenase System in Inflammation

Frank A. D. T. G. Wagener, Hans-Dieter Volk, Dean Willis, Nader G. Abraham, Miguel P. Soares, Gosse J. Adema and Carl G. Figdor
Pharmacological Reviews September 1, 2003, 55 (3) 551-571; DOI: https://doi.org/10.1124/pr.55.3.5
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  • Article
    • Abstract
    • I. Introduction
    • II. Heme
    • III. Heme Oxygenase: The Heme-Degrading Enzyme
    • IV. Inflammation and the Role of Adhesion Molecules
    • V. The Heme-Heme Oxygenase System
    • VI. Conclusion
    • Acknowledgments
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