Publication Date:
2002-06-29
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Eiserich, Jason P -- Baldus, Stephan -- Brennan, Marie-Luise -- Ma, Wenxin -- Zhang, Chunxiang -- Tousson, Albert -- Castro, Laura -- Lusis, Aldons J -- Nauseef, William M -- White, C Roger -- Freeman, Bruce A -- I01 BX000513/BX/BLRD VA/ -- R01 HL067930/HL/NHLBI NIH HHS/ -- R03 TW005682/TW/FIC NIH HHS/ -- New York, N.Y. -- Science. 2002 Jun 28;296(5577):2391-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Internal Medicine, Division of Nephrology, University of California, Davis, CA 95616, USA. jpeiserich@ucdavis.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12089442" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Aorta
;
Catalysis
;
Cattle
;
Cells, Cultured
;
Chromans/metabolism/pharmacology
;
Coculture Techniques
;
Cyclic GMP/metabolism
;
Endothelium, Vascular/enzymology/*physiology
;
Endotoxemia/enzymology
;
Humans
;
Hydrogen Peroxide/metabolism/pharmacology
;
Inflammation/*enzymology/physiopathology
;
Leukocytes/*enzymology
;
Mice
;
Mice, Inbred C57BL
;
Muscle, Smooth, Vascular/metabolism
;
Mutation
;
Nitric Oxide/*metabolism
;
Oxidation-Reduction
;
Peroxidase/genetics/*metabolism
;
Rats
;
Rats, Sprague-Dawley
;
Signal Transduction
;
Transfection
;
Tumor Cells, Cultured
;
*Vasodilation
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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