Myeloperoxidase, a leukocyte-derived vascular NO oxidase.
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.
Eiserich
Jason P
JP
Department of Internal Medicine, Division of Nephrology, University of California, Davis, CA 95616, USA. jpeiserich@ucdavis.edu
Baldus
Stephan
S
Brennan
Marie-Luise
ML
Ma
Wenxin
W
Zhang
Chunxiang
C
Tousson
Albert
A
Castro
Laura
L
Lusis
Aldons J
AJ
Nauseef
William M
WM
White
C Roger
CR
Freeman
Bruce A
BA
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
D002839:Chromans; D009569:Nitric Oxide; D006861:Hydrogen Peroxide; D009195:Peroxidase; D006152:Cyclic GMP; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid