Siglec-1−/FSClow alveolar macrophages exhibit pro-inflammatory phenotypes in chronic obstructive pulmonary disease

Alveolar macrophages (AMs) in patients with chronic obstructive pulmonary disease (COPD) orchestrate persistent inflammation in the airway, however, sub-populations of alveolar macrophages predominantly participating in chronic inflammation have been poorly characterised. We recently reported that Siglec-1 was involved in recognition and engulfment of non-typeable Haemophilus influenzae and that the expression of Siglec-1 on AMs was decreased in COPD lung tissues. Here, based on the expression of Siglec-1 and the intensity of forward scattergram (FSC) using flow cytometry, we identified three subsets present in alveolar macrophages: Siglec-1+/FSChi, Siglec-1−/FSChi, Siglec-1−/FSClow subsets. The Siglec-1−/FSClow subset increased in number in the lungs of COPD subjects. RNA-sequencing revealed that the Siglec-1−/FSClow subset exhibited pro-inflammatory and protease-producing phenotypes compared to other two subsets. Clinically, a decrease in the intensity of Siglec-1 expression in macrophages of induced sputum from COPD subjects was correlated with exacerbation rates in prospective four years. Collectively Siglec-1− AMs showed the pro-inflammatory properties and that their emergence in COPD airways was a risk factor in exacerbation. The Siglec-1−/FSClow subset might serve as “pathogenic macrophages” which could lead to poor clinical outcomes for patients with COPD Examination of monocytes and AMs in control never smoker (CNS), control ex-smoker (CES) and COPD patient