Different faces of the heme-heme oxygenase system in inflammation.
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
Wagener
Frank A D T G
FA
Department of Tumor Immunology, University Medical Center Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. f.wagener@ncmls.kun.nl
Volk
Hans-Dieter
HD
Willis
Dean
D
Abraham
Nader G
NG
Soares
Miguel P
MP
Adema
Gosse J
GJ
Figdor
Carl G
CG
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D019610:Cytoprotection / Q000502:physiology; D004912:Erythrocytes / Q000166:cytology; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D006418:Heme / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000201:enzymology* / Q000503:physiopathology; D018384:Oxidative Stress
D015815:Cell Adhesion Molecules; D006418:Heme; D006419:Heme Oxygenase (Decyclizing)