THE USE OF DEFERIPRONE TO ALLEVIATE IRON LOADING IN MURINE ALVEOLAR-LIKE MACROPHAGES

Alveolar macrophage (AM) iron loading in COPD is associated with worsened pathogen clearance and propagation of the pro-inflammatory phenotype. We have recently shown that the iron chelator deferiprone lowers iron levels in primary human AMs and may improve AM immune function in COPD patients, supporting further exploratory avenues to optimise the pharmacology of using deferiprone as a treatment for enhancing macrophage function in COPD.

This study investigated whether iron loading from different iron sources or experimental COPD could be alleviated using deferiprone in murine AMs. The maximum tolerated dose was also assessed.

Foetal liver alveolar-like macrophages (FLAMs) were treated with ferric-ammonium citrate (30µg/ml), ferrous lactate (10mM), or cigarette smoke extract (10% or 15%) for 16 hours. Treatments were removed and cells were exposed to deferiprone (400µM) for 4 hours. Total cell iron (TCI) levels were assessed by graphite furnace atomic absorption spectroscopy,  iron-related protein expression was assessed by immunoblotting, viability was assessed by alamarBlue assay. Human AMs were treated with deferiprone for 4 or 20 hours and viability was assessed by PrestoBlue assay.

TCI was not decreased in iron-loaded FLAMs treated with deferiprone. Expression of NCOA4 and FTH1 were restored to baseline levels with deferiprone treatment. At the concentrations used in this study, deferiprone did not adversely affect cell viability.

Deferiprone does not appear to decrease iron loading in this model but normalises NCOA4 and FTH1 expression, further highlighting the need for a multifaceted approach to understanding iron metabolism in COPD.