PT  - JOURNAL ARTICLE
AU  - Amy Day
AU  - Peter Barnes
AU  - Louise Donnelly
TI  - COPD monocytes differentiate into pro-inflammatory macrophages regardless of environment
DP  - 2013 Sep 01
TA  - European Respiratory Journal
PG  - P3873
VI  - 42
IP  - Suppl 57
4099  - http://erj.ersjournals.com/content/42/Suppl_57/P3873.short
4100  - http://erj.ersjournals.com/content/42/Suppl_57/P3873.full
SO  - Eur Respir J2013 Sep 01; 42
AB  - COPD is a chronic inflammatory lung disease associated with an increased pro-inflammatory macrophage (mφ) response whereby cells produce increased pro-inflammatory mediators CXCL8 and TNFα and decreased anti-inflammatory mediator IL-10.A monocyte-derived macrophage (MDM) model was used to study the effect of adherence and fetal calf serum (FCS) on mφ phenotype in non-smokers (NS n=3), smokers (S n=3) and COPD patients (COPD n=3).Monocytes were isolated and cultured for 12d in either adherent or non-adherent plates in the presence or absence of FCS and addition of either GM-CSF (G-mφ, M1) or M-CSF (M-mφ, M2). MDM were stimulated for 24h with either LPS or IL-4 and levels of CXCL8, TNFα and IL-10 measured by ELISA.Baseline cytokine production was minimal and did not differ between groups. G-mφ from COPD patients stimulated with LPS produced significantly more TNFα and CXCL8 compared to NS and S (Table 1).View this table:This persisted when G-mφ were cultured without serum or adherence. Lower levels of cytokines were released by M-mφ, although COPD MDM remained pro-inflammatory. M-mφ from S and COPD patients stimulated with IL-4 released less IL-10 than cells from NS (Table 2). This effect was lost in FCS-free media.View this table:COPD MDM consistently produce more pro-inflammatory cytokines and less IL-10 regardless of culture condition. FCS may be priming MDM to produce more cytokines when stimulated ex-vivo. These data suggest that circulating monocytes are primed in patients with COPD to generate a pro-inflammatory mφ regardless of environment.