Myeloperoxidase, a Leukocyte-Derived Vascular NO Oxidase

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Science  28 Jun 2002:
Vol. 296, Issue 5577, pp. 2391-2394
DOI: 10.1126/science.1106830

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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.

  • * These authors contributed equally to this work.

  • To whom correspondence should be addressed. E-mail: jpeiserich{at} or bruce.freeman{at}

  • Present address: Department of Cardiology, University Hospital Eppendorf, Hamburg, Germany.

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