RT Journal Article SR Electronic T1 Different Faces of the Heme-Heme Oxygenase System in Inflammation JF Pharmacological Reviews JO Pharmacol Rev FD American Society for Pharmacology and Experimental Therapeutics SP 551 OP 571 DO 10.1124/pr.55.3.5 VO 55 IS 3 A1 Frank A. D. T. G. Wagener A1 Hans-Dieter Volk A1 Dean Willis A1 Nader G. Abraham A1 Miguel P. Soares A1 Gosse J. Adema A1 Carl G. Figdor YR 2003 UL http://pharmrev.aspetjournals.org/content/55/3/551.abstract AB 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