TY - JOUR T1 - Murine precision cut lung slices as a novel 3D-model for studying endocytic pathways in the lung JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.congress-2021.PA3698 VL - 58 IS - suppl 65 SP - PA3698 AU - Vitalii Kryvenko AU - Andrés Alberro Brage AU - Werner Seeger AU - Susanne Herold AU - Christos Samakovlis AU - István Vadász Y1 - 2021/09/05 UR - http://erj.ersjournals.com/content/58/suppl_65/PA3698.abstract N2 - Introduction: Endocytosis plays a pivotal role in cellular and tissue homeostasis. In the lungs, endocytic mechanisms are involved e.g. in phagocytosis, viral infections and receptor-mediated protein uptake. However, the precise lung cell-specific molecular patterns of endocytosis remain poorly understood. Here, we investigated endocytosis in various lung cell types in precision cut lung slices (PCLS), a viable and fully functional 3D lung tissue model system.Results: By using fluorescent-activated cell sorting (FACS) and confocal microscopy, we studied uptake of different proteins and influenza virus (IV) in PCLS. Our results showed that uptake of albumin, transferrin and IV in epithelial (EpCAM+CD31-CD45-), endothelial (EpCAM-CD31+CD45-) and hematopoietic (EpCAM-CD31-CD45+) cells of PCLS was time- and dose-dependent and of different velocity. Treatment with the endocytosis inhibitor, dynasore, and chlorpromazine, an inhibitor of clathrin-mediated endocytic processes, led to decreased uptake of the cargos and IV in a cell-specific manner. Further differences in endocytic capacity were found, when comparing protein and IV uptake in alveolar epithelial type I and type II cells of PCLS. Moreover, we observed that Ras-related proteins, Rab9 and Rab11, and early endosome antigen-1 (EEA1) played a central role in the uptake of proteins and IV in alveolar epithelial cells from PCLS.Conclusions: Our studies suggest that PCLS might serve as a novel 3D-model for studying endocytic mechanisms in respiratory cells. Understanding the molecular pathways of endocytosis in the lung may provide new therapeutic approaches for patients with pulmonary diseases.FootnotesCite this article as: European Respiratory Journal 2021; 58: Suppl. 65, PA3698.This abstract was presented at the 2021 ERS International Congress, in session “Prediction of exacerbations in patients with COPD”.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only). ER -