LSC Abstract – Macrophage phenotype changes within the small airway wall in smokers and chronic obstructive pulmonary disease

Abstract

Hypocellularity in the large airway wall has recently been described in mild-moderate COPD. We investigated macrophage populations in the small airway lamina propria (LP) and Epithelium (Ep) of mild to moderate COPD patients using surgically resected tissue (SRT), with a mix of current smokers (COPD-CS) and ex-smokers (COPD-ES). As controls we had SRT from normal lung function smokers (NLFS) and normal controls (NC). Tissues were immuno-stained for M2 (anti-inflammatory) macrophages (CD163) and M1 (pro-inflammatory) macrophages (inducible nitric oxide synthase, iNOS plus CD68). Numbers were enumerated in the Ep and SA-LP (to 100µm deep); cells per millimetre (mm) and cells per mm2 of airway wall were calculated respectively. SA walls have higher numbers of total CD68+ macrophages than previously seen in large airways but with no difference between any groups. LP: In normals there were very few M1 macrophages; In smokers and COPD a large expansion of M1 macrophages. M2 macrophages were little affected by smoking, but were reduced in COPD groups. The average ratios of M2 cells to M1 cells were 12:1 in NC, 1.5:1 in NLFS, 0.5:1 in COPD-CS and 2:1 in COPD-ES. Ep: There was a complete change of cell type predominance in the differentiated macrophages with 8% M2 cells in the normal and 0% M1 cells, yet hardly any M2 cells in the pathological groups but with expansions in M1 cells (24% COPD-CS). This is the first cross-sectional human study to report on macrophage subsets across these phenotypic groups. The activation, differentiation and emergence of M1 macrophages in LP appears to be a smoking effect, whilst the decline of M2 macrophages appears mostly a COPD-related effect. Percentage of M0, M1 and M2 cells per total macrophage population Percentage of macrophage populations in the epithelium and lamina propria of COPD-CS and Normal controls