Contributions of myeloperoxidase to proinflammatory events: More than an antimicrobial system

Optimal oxygen-dependent antimicrobial activity of circulating polymorphonu clear leukocytes reflects the synergistic effects of the myeloperoxidase (M PO)-hydrogen peroxide-halide system. Delivered from its storage compartment to the phagolysosome during fusion of the azurophilic granules, MPO cataly zes the oxidation of chloride in the presence of H2O2, chemistry unique to MPO, and thereby generates an array of highly reactive oxidants. Recent inv estigations of a wide range of inflammatory disorders have identified bioch emical markers of MPO-dependent reactions, thus indirectly implicating MPO in their pathogenesis, progression, or perpetuation. The implied involvemen t of MPO-dependent events in diseases such as atherosclerosis forces reexam ination of several fundamental tenets about MPO that are derived from studi es of myeloid cells, most notably factors important in the regulated expres sion of MPO gene transcription. The evidence supporting a role for MPO in t he pathogenesis of atherosclerosis, demyelinating diseases of the central n ervous system, and specific cancers is reviewed and some of the new questio ns raised by these studies are discussed. Lastly, an appreciation for the e xistence of a broad family of proteins structurally related to MPO and the functional diversity implied by the corresponding structures may provide in sights into novel ways in which MPO can function as more than an important antimicrobial component. (C) 2001 The Japanese Society of Hematology.