Phagocytotic impairment of tissue-resident alveolar macrophages by diesel particulates drives pulmonary surfactant accumulation

Abstract

Airborne particulate matter, particularly diesel particulate matter (DPM), is a major component of air pollution and poses significant risks to lung health. Tissue-resident alveolar macrophages (TR-AMs), which dominate the immune landscape of the alveoli, are essential for immune surveillance and pulmonary surfactant homeostasis. While previous studies have reported detrimental effects of particulate matter on macrophages, little effort has been made to its impact on the key physiological functions—chemotaxis and phagocytosis—of TR-AMs, the most predominant macrophage lineage in the lung. We found that DPM exposure markedly altered gene expression profiling in murine TR-AM cell line MH-S, notably downregulating genes related to cytoskeleton actin dynamics, chemotaxis, and bacterial recognition. Both MH-S cells and primary TR-AMs displayed impaired migration and phagocytosis of Escherichia coli and Staphylococcus aureus, associated with reduced filamentous actin (F-actin) polymerization and filopodia formation. Cytochalasin D treatment further confirmed the role of actin remodeling in bacterial engulfment. In vivo, DPM exposure reduced the proportion of highly phagocytic TR-AMs, accompanied by inefficient clearance of pulmonary surfactant, leading to accumulation of Periodic acid-Schiff-positive granules, elevated surfactant protein D, and excessive lipids in both alveoli and bronchoalveolar lavage fluid (BALF). Further compositional analysis of BALF revealed excessive accumulation of phosphatidylcholine, ceramide, and cholesterol in DPM-exposed mice. In conclusion, DPM disrupts F-actin–dependent migration and phagocytosis in TR-AMs, undermining alveolar immune surveillance and surfactant homeostasis. These results highlight a key mechanism by which air pollution compromises lung defense, offering insight into particulate matter–related respiratory disease pathogenesis.

Keywords

Diesel particulate matter / Alveolar macrophages / Chemotaxis / Phagocytosis / Pulmonary surfactant

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Funding

Guangdong Basic and Applied Basic Research Foundation(2022A1515012228)

Guangdong Science and Technology Department(2023B1212060028)

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The Author(s)