Myeloperoxidase controls NO and vascular tone

Myeloperoxidase (MPO) is an abundant phagocyte hemoprotein with well-established microbicidal functions in vitro, but its role in blood infections has been unclear. In 28 June Science, Jason Eiserich and colleagues from University of California, Davis, USA, show that leukocyte-derived myeloperoxidase is a vascular NO oxidase that can directly modulate vascular inflammatory responses by regulating NO bioavailability (Science 2002, 296:2391-2394).

Eiserich et al. worked with a rodent model of acute inflammation (endotoxemia) and observed that after leukocyte degranulation, MPO localize in and around vascular endothelial cells. Wild type mice had impaired endothelium-dependent relaxant responses, but MPO-deficient mice showed no alteration in vascular responses. In addition, they show that in wild type mice MPO generated substrate radicals that caused a catalytic consumption of NO, which could explain the perturbed vascular responsiveness.

"Drugs aimed at mimicking this enzymatic activity may be useful for treating systemic hypotension during septic shock. Alternatively, drugs aimed at ...