Scheme 1.

Schematic showing the release of MPO from inflammatory cells within the synovial tissue and the chlorination of cartilage matrix proteins. ROS formation is a dynamic process that relies on the initial consumption of oxygen from the microenvironment and its conversion to ${\mathrm{O}}_2^{.-}$. The production of ${\mathrm{O}}_2^{.-}$ by neutrophils and monocytes/macrophages is initiated by the activation assembly of NADPH-oxidase. ${\mathrm{O}}_2^{.-}$ undergoes spontaneous dismutation to hydrogen peroxide (H₂O₂) in the presence of hydrogen ions at a rate of 5.0 × 10⁵ M⁻¹s⁻¹ at pH 7.0–7.2. H₂O₂ is then utilized as a substrate in the myeloperoxidase (MPO)/halide catalyzed reaction producing hypochlorous acid (HOCl), a highly reactive oxygen species, and in the presence of chloride ions at pH 4–5.5, highly reactive chlorine gas (Cl₂). The reaction of HOCl and Cl₂ with cartilage components, such as tyrosine, tryptophan, lysine, and pyridinoline crosslinks, and subsequent proteolytic cleavage would result in the generation of chlorinated-peptides.