How the lung deals with oxidants.

Oxidants are compounds capable of withdrawing electrons from target atoms or molecules, thus initiating chemical reactions. In biological systems, oxidative modifications are often related to structural, functional and regulatory changes. Partially reduced oxygen species, also known as oxygen-derived free radicals, represent the most important group of biologically relevant oxidants. Significant amounts of oxygen-derived free radicals are produced by inflammatory cells, capable of destroying neoplastic tissue, altering cellular function, modulating inflammation and exhibiting antimicrobial defence. In the lung, reactive oxygen metabolites mainly originate from alveolar macrophages and, during inflammation, also from invading neutrophils and eosinophiL-;. Phagocytic cells are endowed with a complex enzyme system located in the plasma membrane, the nicotinamideadenine-dinucleotide phosphate (reduced form) (NADPH) (or burst) oxidase [1], which is dormant in silent cells, but activated in stimulated cells to catalyse the reduction of molecular oxygen to the superoxide anion (0 2 ' ). In a subsequent step, o2· dismutates to hydrogen peroxide (Hp 2 ) and molecular oxygen, catalysed by the enzyme superoxide dismutase. In the presence of metal ions, highly reactive hydroxyl radicals (OR) arise from 0 2 and ~02 via the Haber-Wciss or Fenton reaction, respectively [2]. Hydroxyl radicals are also formed by neutrophils and monocytes from H 2 0 2 in a myeloperoxidase-dependent reaction [3]. However, the main function of myeloperoxidase from neutrophils (and chloroperoxidase from eosinophils) is the formation of cytotoxic hypochlorous acid (HOC!), a process which also consumes Hp 2 •