Fig. 1. Myeloperoxidase (MPO) and peroxynitrite pathways to produce nitrotyrosine are shown. The treatment with lipopolysaccharide (LPS) sequesters neutrophils (PMN) in the lungs, thereby activating the MPO or peroxynitrite pathways to produce nitrotyrosine; chloro-tyrosine is also produced by myeloperoxidase activity. LPS treatment induces inducible nitric oxide synthase (iNOS) in pulmonary alveolar macrophage (PAM) and type 2 cells, increasing nitric oxide (NO) levels, which combine with superoxide, thereby giving rise to peroxynitrite. LPS treatment also induces iNOS in alveolar macrophages, thereby activating the peroxynitrite pathway, which results in production of nitrotyrosine without chlorotyrosine. The detection of nitrotyrosine together with chlorotyrosine indicates that the myeloperoxidase pathway has a role in the production of the nitrotyrosine, whereas detection of nitrotyrosine in the absence of chlorotyrosine indicates that the peroxynitrite pathway mainly contributes to the production of nitrotyrosine.