Haem oxygenase-1 polymorphism and ARDS, friend and foe?

Excerpt

Acute lung injury (ALI) and its extreme manifestation, acute respiratory distress syndrome (ARDS), complicate a wide variety of serious medical and surgical conditions, not all of which affect the lung directly [1]. The incidence of ALI increases with age, and around 190,600 cases occur in the United States alone each year [2]; these represent only a small proportion of those at risk. It therefore seems likely that genetic factors may render individuals susceptible to ALI. The pathogenesis of ALI/ARDS remains incompletely understood, but oxidative stress is implicated as a contributory factor to the onset and progression of disease in that the production of reactive oxygen species (ROS) influences both pro- and anti-inflammatory cell-signalling pathways. Additionally, the conversion of ROS to more aggressive species by iron catalysis can damage bio-molecules and cells directly [3]. The haem oxygenases (HO) are potent anti-inflammatory and anti-oxidative enzymes that catalyse the degradation of haem to biliverdin, carbon monoxide (CO) and free iron [4]. The inducible isoform HO-1 is thought to be cytoprotective under pro-oxidative conditions. The mechanism of this is unknown but probably acts through the properties of biliverdin and bilirubin and the anti-inflammatory effects of CO [5]. However, reactive ferrous iron produced during the catabolism of haem by HO may catalyse oxidative damage [6]. Thus, HO-1 induction may be protective or deleterious, depending on several factors including substrate availability and levels of protein expression. …