Enhancing Pulmonary Particle Clearance by Redirecting Alveolar Macrophages: A therapeutical Study Using a new SiglecF-cre Lineage Tracing System

Keywords: Alveolar Macrophages, Chemokines, Pulmonary Clearance, Lineage Tracing, SiglecF-cre Background: Alveolar macrophages (AMs) play a critical role in clearing inhaled particles from the lung. Traditionally considered sessile, recent evidence suggests their migratory behavior may be reprogrammable under certain conditions. This study investigates whether AMs can be redirected from the alveolar space to the mucociliary escalator to enhance pulmonary clearance. Methods: Using SiglecF-cre×Ai14 mice, we trace AM positioning via tdTomato expression validated by flow cytometry, immunohistochemistry, and intravital microscopy. A panel of chemokines (e.g., CCL2, CCL4, CCL7) will be screened in vitro using Boyden chamber assays (MHS cells and primary AMs) to identify selective chemoattractants. The most specific chemokine will be aerosol-delivered to induce AM emigration in vivo. Particle clearance will be assessed via fluorescent nanoparticle tracking, and inflammation evaluated through cytokine profiling and BAL analysis. Preliminary Results: Initial scRNAseq and array data comparisons show differential CCR expression between MHS and primary AMs. CCR2 and CCR5 were highly expressed, supporting CCL2/CCL4 as strong candidates. Feasibility of aerosol delivery and AM visualization techniques has been established in the host lab. Conclusion: Redirecting AM positioning through chemokine-mediated migration offers a novel therapeutic strategy for enhancing lung particle clearance. This approach may serve as a non-depletive alternative to macrophage ablation in managing environmental lung exposures. Publication History Article published online: 04 March 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany