title: Myeloperoxidase, a leukocyte-derived vascular NO oxidase.
abstract: Myeloperoxidase (MPO) is an abundant mammalian phagocyte hemoprotein thought to primarily mediate host defense reactions. Although its microbicidal functions are well established in vitro, humans deficient in MPO are not at unusual risk of infection. MPO was observed herein to modulate the vascular signaling and vasodilatory functions of nitric oxide (NO) during acute inflammation. After leukocyte degranulation, MPO localized in and around vascular endothelial cells in a rodent model of acute endotoxemia and impaired endothelium-dependent relaxant responses, to which MPO-deficient mice were resistant. Altered vascular responsiveness was due to catalytic consumption of NO by substrate radicals generated by MPO. Thus MPO can directly modulate vascular inflammatory responses by regulating NO bioavailability.
authors.affiliation: Department of Internal Medicine, Division of Nephrology, University of California, Davis, CA 95616, USA. jpeiserich@ucdavis.edu
authors.forename: Jason P
authors.initials: JP
authors.lastname: Eiserich
authors.forename: Stephan
authors.initials: S
authors.lastname: Baldus
authors.forename: Marie-Luise
authors.initials: ML
authors.lastname: Brennan
authors.forename: Wenxin
authors.initials: W
authors.lastname: Ma
authors.forename: Chunxiang
authors.initials: C
authors.lastname: Zhang
authors.forename: Albert
authors.initials: A
authors.lastname: Tousson
authors.forename: Laura
authors.initials: L
authors.lastname: Castro
authors.forename: Aldons J
authors.initials: AJ
authors.lastname: Lusis
authors.forename: William M
authors.initials: WM
authors.lastname: Nauseef
authors.forename: C Roger
authors.initials: CR
authors.lastname: White
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Freeman
mesh_terms: D000818:Animals; D001011:Aorta; D002384:Catalysis; D002417:Cattle; D002478:Cells, Cultured; D002839:Chromans / Q000378:metabolism / Q000494:pharmacology; D018920:Coculture Techniques; D006152:Cyclic GMP / Q000378:metabolism; D004730:Endothelium, Vascular / Q000201:enzymology / Q000502:physiology*; D019446:Endotoxemia / Q000201:enzymology; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology; D007249:Inflammation / Q000201:enzymology* / Q000503:physiopathology; D007962:Leukocytes / Q000201:enzymology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D009154:Mutation; D009569:Nitric Oxide / Q000378:metabolism*; D010084:Oxidation-Reduction; D009195:Peroxidase / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D014162:Transfection; D014407:Tumor Cells, Cultured; D014664:Vasodilation
chemical_list: D002839:Chromans; D009569:Nitric Oxide; D006861:Hydrogen Peroxide; D009195:Peroxidase; D006152:Cyclic GMP; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid