Background and Aims

Iron levels are increased in the airways of COPD patients. We have shown red blood cell coverage in the alveolar space is increased in COPD. Heme (red blood cell-derived iron) recruits neutrophils and leads to harmful neutrophil extracellular trap production. We investigated whether iron dysregulation is associated with neutrophilic inflammation in COPD.

Methods

We analysed iron metabolism gene expression in sputum cells, bronchial brushings and bronchoalveolar lavage (BAL) cells from COPD patients (n=30) by RNA sequencing. We compared the expression of genes involved in iron metabolism in neutrophil high (neutrophils ?3% of BAL cells) and neutrophil low (neutrophils <3% of BAL cells) patients; n=14 vs n=16 respectively. Levels of proteins involved in iron metabolism were measured in BAL fluid (BALF).

Results

Gene expression of extracellular iron binding proteins was significantly increased in BAL cells from neutrophil high patients: Lactoferrin, Ceruloplasmin and Lipocalin-2 (2.14, 1.79 and 1.57-fold increase respectively) (p<0.05 for all). At the protein level, iron binding proteins were increased in BALF from neutrophil high patients: Lactoferrin and Haptoglobin (4.67 and 117.93-fold increase respectively) (p<0.05 for both). Neutrophil high patients had decreased expression of genes associated with heme metabolism, mitochondrial iron storage and heme synthesis in BAL cells. There were no consistent gene expression changes in sputum or bronchial brushings.

Conclusion

Neutrophilic inflammation is associated with dysregulated iron metabolism in BAL cells from COPD patients. Neutrophils and iron levels have an interconnected relationship in COPD.