LSC Abstract – GM-CSF drives human lung tissue macrophages towards a more pro-inflammatory phenotype

COPD is associated with elevated matrix metalloprotease-9 (MMP9) and pro-inflammatory cytokines, e.g. TNFα, which may be derived from macrophages (mΦ). Altering mΦ phenotype towards a resolving cell maybe therapeutic. GM-CSF and M-CSF are used during differentiation of monocytes in vitro to influence phenotype, thus this study assessed whether GM-CSF or M-CSF could alter mature mΦ phenotype. Human lung tissue mΦ (TmΦ) from controls (C;n=5) and COPD patients (n=5) were cultured in media alone or with GM-CSF or M-CSF for 6d to assess plasticity. Levels of TNFα were measured by ELISA after 24h stimulation with LPS (10ng/ml) and MMP9 expressing by RTqPCR. Basal release of TNFα did not differ between culture conditions or subject group but following LPS stimulation, TmΦ cultured in GM-CSF had significantly (p<0.01) higher TNFα release compared to mΦ cultured in media, with M-CSF having no effect (Fig 1A). MMP9 expression did not change between culture conditions for any subject group (Fig 1B), however there is a trend towards higher TNFα and MMP9 in COPD TmΦ compared to control. TmΦ can be manipulated by GM-CSF towards a more inflammatory phenotype, although this is limited to changes in TNFα. Elevated GM-CSF in COPD patients may be driving altered mΦ phenotype, thus targeting the GM-CSF driven phenotype might be a novel anti-inflammatory strategy. Changes in TNFα and MMP9