Impact of particulate matter (PM) exposure on lung macrophage phenotype and phagocytic activity

Abstract

Background: Epidemiologic studies have shown that particulate matter (PM10) increase pulmonary morbidity and mortality. Lung macrophages (LM) are key first-line immune effector cells phagocytosing and processing inhaled PM10. LM phenotypes (M1 which are more pro-inflammatory and M2 more anti-inflammatory promoting tissue repair) role and responses in processing PM is still unclear. The goal of this study was to evaluate the phagocytic function of different macrophage phenotypes following exposure to urban air pollution particles.

Methods: PMA was use to differentiate THP-1 monocytes into macrophages (M0) and further into M1 mac's with INF-λ and LPS and M2 mac's using IL-4 and IL-13. Surface marker labelling (CD68, CD206, CD163 and CD80) and flow cytometry were used to quantify different populations. Urban PM10 (EHC93) phagocytosis were quantify and mediator production measure. The impact of PM10 on phagocytosis of Staph Aureus were measured.

Results: PM10 exposure increase M1 (13 to 19 to 28% with 0, 0.03mg/ml and 0.05mg/ml PM) and decrease M2 differentiation in a dose depended manner. PM10 were phagocytosed the best by M1 mac'ss with less phagocytosis by M2 mac's (22.4±3.2vs 10.5±2.1%, p<0.05). M1 mac's produce IL-1β, IL-6 and TNF-α, while M2 mac's produce IL-10, IL-1RA and CCL-22 in a dose dependent manner. PM10 reduces M1 mac's phagocytosis of Staph Aureas (76±8%vs48±9%vs41±5% with 0, 0.03mg/ml and 0.05mg/ml PM respectively, p<0.001) in a dose dependent manner with no effect on M2 macrophages.

Conclusions: Urban particle exposure skewed macrophages to a M1 phenotype but also suppress their phagocytosis of bacteria, suggesting it promote vulnerability to lung infection/colonization.