Contributions of myeloperoxidase to proinflammatory events: more than an antimicrobial system.
Optimal oxygen-dependent antimicrobial activity of circulating polymorphonuclear leukocytes reflects the synergistic effects of the myeloperoxidase (MPO)-hydrogen peroxide-halide system. Delivered from its storage compartment to the phagolysosome during fusion of the azurophilic granules, MPO catalyzes the oxidation of chloride in the presence of H2O2, chemistry unique to MPO, and thereby generates an array of highly reactive oxidants. Recent investigations of a wide range of inflammatory disorders have identified biochemical markers of MPO-dependent reactions, thus indirectly implicating MPO in their pathogenesis, progression, or perpetuation. The implied involvement of MPO-dependent events in diseases such as atherosclerosis forces reexamination of several fundamental tenets about MPO that are derived from studies of myeloid cells, most notably factors important in the regulated expression of MPO gene transcription. The evidence supporting a role for MPO in the pathogenesis of atherosclerosis, demyelinating diseases of the central nervous system, and specific cancers is reviewed and some of the new questions raised by these studies are discussed. Lastly, an appreciation for the existence of a broad family of proteins structurally related to MPO and the functional diversity implied by the corresponding structures may provide insights into novel ways in which MPO can function as more than an important antimicrobial component.
Nauseef
W M
WM
Inflammation Program and Departments of Medicine, University of Iowa and Veterans Administration Medical Center, Iowa City 52242, USA. william-nauseef@uiowa.edu
D000818:Animals; D000890:Anti-Infective Agents; D001161:Arteriosclerosis / Q000201:enzymology / Q000209:etiology; D002493:Central Nervous System Diseases / Q000201:enzymology / Q000209:etiology; D006801:Humans; D006997:Hypochlorous Acid / Q000378:metabolism; D007249:Inflammation / Q000201:enzymology* / Q000209:etiology; D009195:Peroxidase / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D000890:Anti-Infective Agents; D006997:Hypochlorous Acid; D009195:Peroxidase