Abstract
BackgroundAlveolar macrophages are professional phagocytes that remove microbial pathogens inhaled into the lung. The phagocytic ability is compromised in chronic obstructive pulmonary disease (COPD). However, the molecular mechanisms underlying this defect in phagocytosis are not clearly defined.Materials and methodsCell suspensions were collected from lung tissues of patients undergoing lung resection. Alveolar macrophages were detected as FSChi/ SSChi/CD45+/CD206+ cells in the isolated cell suspension by flow-cytometry. The cell surface expression of plasma membrane-bound phagocytic receptors (Fcγ receptor I (FcγRI), a complement receptor CD11b, macrophage scavenger receptor-1 (MSR-1), CD36 and Siglec-1) was determined on the alveolar macrophages. Correlations between the expression levels of the phagocytic receptors and disease severity were analysed. Phagocytosis of fluorescence-tagged bacteria by human alveolar macrophages was evaluated.ResultsThe flow-cytometry analyses revealed that FcγRI, CD11b, MSR-1 and Siglec-1, but not CD36, were expressed on human alveolar macrophages. Among these receptors, Siglec-1 expression was significantly decreased on alveolar macrophages in COPD ex-smokers (n = 11), compared to control never-smokers (n = 11) or control ex-smokers (n = 9). The Siglec-1 expression on alveolar macrophages was significantly correlated with lung function (forced expiratory volume in 1 s) and with the severity of emphysema. Treatment of human alveolar macrophages with an anti-Siglec1 blocking antibody decreased phagocytosis of non-typeable Haemophilus influenzae (NTHi).ConclusionOur findings demonstrated reduced expression of Siglec-1 on alveolar macrophages in COPD, which is involved in engulfment of NTHi.
Highlights
Alveolar macrophages are professional phagocytes that remove microbial pathogens inhaled into the lung
The Siglec-1 expression on alveolar macrophages was significantly correlated with lung function and with the severity of emphysema
Characterisation of phagocytosis-associated receptor expression on alveolar macrophages isolated from lung tissues of patients with chronic obstructive pulmonary disease (COPD) To examine cell surface expression levels of phagocytosis-associated receptors on human alveolar macrophages, we collected cell suspension by perfusing and lavaging peripheral lung tissues with saline and delineated alveolar macrophages as FSChi/SSChi/CD45+/ CD206+ cells in flow-cytometry according to previous studies [2, 3] (Fig. 1a)
Summary
Alveolar macrophages are professional phagocytes that remove microbial pathogens inhaled into the lung. Plasma membrane-receptors have a critical role in the sensing and engulfment of microbes in the initial phase of phagocytosis and are classified into (i) opsonic receptors (Fc receptors and complement receptors) and (ii) nonopsonic, pattern-recognition receptors (scavenger receptors and lectin-like recognition molecules) [9] Scavenger receptors such as macrophage scavenger receptor-1 (MSR-1, known as SR-A1), macrophage receptor with collagenous structure (MARCO, known as SRA2) and CD36 vary in the structure of their extracellular domains and recognise a large variety of molecules including microbial ligands (lipopolysaccharide and lipoteichoic acid) and endogenous self-ligands (lipoproteins, unmodified proteins, etc.) [10]. Lectin-like recognition molecules consist of diverse membranebound receptors such as C-type lectin receptors (mannose receptor or dectin-1, etc.) and sialic acid-binding immunoglobulin-like lectins (e.g. Siglec-1) [11] This extremely diverse array of plasma membrane-receptors allows professional phagocytes to sense and eat a wide variety of foreign pathogens
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
