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Cyclic Strain and Macrophage‐Mediated Transport Govern Micron‐Sized PM 2 . 5 Translocation across the Air–Blood Barrier

Year: 2025
Type: article
Abstract: PM 2 . 5 translocated across the air‐blood barrier (ABB) can accumulate in the lungs and extrapulmonary organs, leading to both pulmonary and systemic pathophysiological effects. However, the mechanisms governing the translocation of micron‐sized PM 2 . 5 (MPs) remain unclear. Here, a physiologically relevant in vitro ABB model is developed, comprising a triple co‐culture system under respiratory‐like cyclic strain. Using this platform, it is demonstrated that cyclic stretching enhances dTHP‐1 phagocytosis and transmigration, synergistically promoting macrophage‐mediated MPs translocation across the ABB in combination with strain‐induced disruption of epithelial tight junctions. This cooperative mechanism governs MPs translocation across the ABB and markedly increases the transport of 2 µm particles compared to static conditions. By using scavenger receptor A (SR‐A) inhibitors, this process are confirmed to be predominantly driven by macrophage phagocytosis. Furthermore, this study explores the potential fate of particles post‐translocation, proposing their subsequent release from macrophages via active lysosomal exocytosis and passive release mediated by cell death. These findings provide new insights into mitigating PM 2 . 5 ‐induced health risks and inform macrophage‐assisted pulmonary drug delivery strategies.
Language: English
Open Access status: gold
Estimated APC paid: $6,730
OpenAlex ID: W4415675767
FWCI: 1.625
Cites: 83
Cited by: 4
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