Clotting revisited

Ancient Greek philosophers extolled moderation in all things. On page 283, Minamoto and colleagues show that carbon monoxide (CO) inhalation is no exception. In a mouse model of trachea transplantation, inhaled CO—in moderation—prevented the development of lethal obstructive airway disease. CO gas is both a toxic air pollutant and a normal byproduct of cellular heme metabolism. Although CO is well-known for its role as an asphyxiant, recent studies have revealed its virtues, which include anti-inflammatory and anti-apoptotic effects on a variety of cell types. CO has also been shown to inhibit the rejection of xenogeneic heart transplants in rats. Minamoto et al. now add to that list of virtues by showing that treating mice with low-dose inhaled CO reduced the T cell infiltration and airway obstruction that develops after allogeneic tracheal transplantation. The benefits of endogenous CO were evident based on comparisons with mice that received grafts lacking the CO-synthesizing enzyme hemoxygenase-1 (Hmox-1), which developed more severe disease than mice that received wild-type grafts. This group previously showed that the development of post-transplant airway obstruction requires the expression of inducible nitric oxide synthase (iNOS). They now find that CO counterbalances the production of nitric oxide by inhibiting the activation of the transcription factor NFB, which drives the expression of iNOS. This came as a surprise to the authors, as most other known effects of CO depend on activation of the MAP kinase or cyclic GMP signaling pathways. Further experiments are required to determine how CO inhibits NFB activation. But in the meantime, these data suggest that increasing endogenous CO levels might be therapeutic in transplant patients who develop a lethal, and currently untreatable, complication of lung transplantation called obliterative bronchiolitis. Inhaled carbon monoxide reduces T cell (brown) invasion of the airways following allogeneic tracheal transplantation. Clotting revisited