Healthy pulmonary macrophages (mΦ) respond to environmental change by altering their phenotype. In COPD, mΦ are phenotypically distinct with increased pro-inflammatory mediator release and defective phagocytosis. The reasons for this are unclear, but the growth factors GM-CSF and M-CSF can determine mΦ differentiation.
We generated monocyte-derived macrophages (MDM) from non-smokers (NS=5), smokers (S=4) and COPD patients (COPD=5) using GM-CSF (GmΦ) or M-CSF (MmΦ) and then examined plasticity by switching culture conditions. Phagocytosis of Streptococcus pneumoniae (SP) and Haemophilus influenzae (HI) was measured fluorometrically at baseline, 2, 4 and 6 days post-switching.
Baseline MmΦ phagocytosed more SP and HI than GmΦ in all subject groups (NS 170±40%, S 180±60%, COPD 110±20%). Switching to M-CSF significantly increased phagocytosis in non-smokers (SP:280±25% HI:200±40%) (p<0.05) but to a far lesser extent in smokers (SP:170±30% HI:70±50%) and COPD mΦ (SP:2%±1% HI:50±20%) by day 6. Switching to GM-CSF for decreased phagocytosis by half in all subject groups.
As GM-CSF suppressed phagocytosis, GM-CSF and M-CSF sputum levels were analysed using ELISA. GM-CSF was significantly higher in COPD sputum (183±32pg/ml, n=9) compared to sputum from non-smokers (47±3pg/ml, n=5) and smokers (36±4pg/ml, n=8) (p<0.05). M-CSF was lower in sputum from COPD patients (14±7pg/ml, n=9) and smokers (9±4pg/ml, n=8) compared to sputum from non-smokers (22±12pg/ml, n=5).
Regardless of culture changes, COPD macrophages retain phagocytic defects indicating lack in plasticity. This may be further exacerbated by a pro-inflammatory, GM-CSF-rich lung environment.
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