Altered scavenger receptor expression and response to oxidative stress is linked to defective bacterial phagocytosis in COPD macrophages

Alveolar macrophages (Mφ) from COPD patients show defective bacterial phagocytosis, which may be linked to increased oxidative stress in the lungs. Scavenger receptors mediate phagocytosis, but may become damaged by oxidative stress. In this study, the effect oxidative stress on phagocytosis and cell surface receptor expression was studied in monocyte-derived Mφ (MDM). MDM from non-smokers (NS), smokers (S) or COPD patients were cultured in GM-CSF for 12 d (n=5-7), then treated ± 200µM H₂O₂ for 24h. MDM were exposed to fluorescently labelled <i>H.influenzae</i> (HI) or <i>S.pneumoniae</i> (SP) for 4 h, labelled with antibodies for HLA-DR, CD36, CD80, CD163, CD206, α_vβ₃ and ICAM-3, and analysed by flow cytometry. At baseline, COPD MDM expressed 68% less HLA-DR compared to NS (p&lt;0.05). In NS and S MDM, phagocytosis of HI, increased expression of CD80 (NS 229%, S 797%, p&lt;0.05), α_vβ₃ (NS 354%, S 313%, p&lt;0.05), and ICAM-3 (NS 248%, S 892%, p&lt;0.01). In COPD MDM, phagocytosis did not change receptor expression. H₂0₂ decreased phagocytosis of HI (NS 35%, S 16%, COPD 17% p&lt;0.05) and SP (NS 54%, S 30%, COPD 43%, p&lt;0.05). In NS MDM only, H₂0₂ caused a decrease in ICAM-3 expression after HI phagocytosis (37% p&lt;0.05), but had no effect on other receptors. MDM from COPD patients display differential scavenger receptor profiles compared to healthy MDM in response to phagocytosis of bacteria. This could contribute to Mφ dysfunction in COPD. Exogenous oxidative stress decreased phagocytosis in all patient groups, which may be linked to decreased expression of ICAM-3. Identifying the mechanisms involved in receptor expression may prove advantageous in developing novel therapies.