Free radical pathways of macromolecular damage and tissue destruction - some topical examples

Free radical pathways of macromolecular damage and tissue destruction - some topical examples 

Inactivation of serpins and activation of latent metalloproteinases in pulmonary emphysema and rheumatoid arthritis 

Pulmonary emphysema is associated with cigarette smoking in normal individuals, as well as with ajAT deficiency. In smokers, though absolute levels of aiAT are normal, elastase inhibitory activity is depressed [93]. This is due to the oxidation of a critical, reactive centre, methionine residue (met 358) to methionine sulphoxide [94], Likewise, a large proportion of aiAT is also inactivated in the rheumatoid joint cavity [95,96], even when synovial fluid samples are analysed immediately after aspiration [97]. Again, 

Since aiAT represents the archetype for the serpin (serine-proteinase inhibitor) superfamily of proteins, it is possible that similar oxidative or proteolytic mechanisms may function in the inactivation of other serpins that are important in controlling the inflammatory cascade. Some serpins contain a readily oxidised reactive-centre methionine residue (e.g. plasminogen activator-inhibitor [108] and a2-antiplasmin [109]), whilst all serpins (including antithrombin III [110] and protease nexin I [111]) contain an exposed loop which is susceptible to cleavage by proteinases. 

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