Dysregulation of the CD163-Haptoglobin Axis in the Airways of COPD Patients

Pulmonary iron levels are increased in chronic obstructive pulmonary disease (COPD) patients. Iron causes oxidative stress and is a nutrient for pathogenic bacteria. Iron may therefore play an important role in the pathophysiology of COPD. The CD163-haptglobin axis plays a central role in the regulation of iron bioavailability. The aim of this study was to examine dysregulation of the CD163-haptglobin axis in COPD. We measured soluble CD163 (sCD163) and haptoglobin levels in sputum supernatants by enzyme-linked immunosorbent assay (ELISA) and sputum macrophage CD163 and haptoglobin expression by flow cytometry in COPD patients and controls. SCD163 levels were lower in COPD patients compared to controls (p = 0.02), with a significant correlation to forced expiratory volume in 1 s (FEV1)% predicted (rho = 0.5, p = 0.0007). Sputum macrophage CD163 expression was similar between COPD patients and controls. SCD163 levels and macrophage CD163 expression were lower in COPD current smokers compared to COPD ex-smokers. Haptoglobin levels were not altered in COPD patients but were regulated by genotype. Macrophage CD163 and haptolgobin expression were significantly correlated, supporting the role of CD163 in the cellular uptake of haptoglobin. Our data implicates a dysfunctional CD163-haptoglobin axis in COPD, which may contribute to disease pathophysiology, presumably due to reduced clearance of extracellular iron.

Automated summary

This study found that pulmonary iron levels are increased in chronic obstructive pulmonary disease (COPD) patients, which may play an important role in the pathophysiology of COPD. The dysregulation of the CD163-haptoglobulin axis in COPD was examined, and it was found that soluble CD163 levels were lower in COPD patients compared to controls, with a significant correlation to forced expiratory volume in 1 s (FEV1)% predicted. The study also revealed a correlation between macrophage CD163 expression and haptoglobin levels, supporting the role of CD163 in the cellular uptake of haptoglobin.