An investigation of the resolution of inflammation (catabasis) in COPD

Chronic Obstructive Pulmonary Disease (COPD) is characterized by an enhanced inflammatory response to smoking that persists despite quitting. The resolution of inflammation (catabasis) is a complex and highly regulated process where tissue resident macrophages play a key role since they phagocytose apoptotic cells (efferocytosis), preventing their secondary necrosis and the spill-over of their pro-inflammatory cytoplasmic content, and release pro-resolution and tissue repair molecules, such as TGFβ, VEGF and HGF. Because inflammation does not resolve in COPD, we hypothesized that catabasis may be abnormal in these patients.

To explore this hypothesis, we studied lung tissue samples obtained at surgery from 21 COPD patients, 22 smokers with normal spirometry and 13 non-smokers controls. In these samples we used: (1) immunohistochemistry to assess the expression of CD44, CD36, VEGF and TGFβ in lung macrophages; (2) real time PCR to determine HGF, PPARγ, TGFβ, VEGF and MMP-9 gene expression; and, (3) ELISA to quantify lipoxin A4, a lipid mediator of catabasis.

We found that current and former smokers with COPD showed: (1) more inflammation (higher MMP-9 expression); (2) reduced macrophage surface expression of CD44, a key efferocytosis receptor; and, (3) similar levels of TGFβ, VEGF, HGF, PPARγ, and lipoxin A4 than smokers with normal spirometry, despite the presence of inflammation and disease.

These results identify several potential abnormalities of catabasis in patients with COPD.