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Clathrin-Mediated Albumin Clearance in Alveolar Epithelial Cells of Murine Precision-Cut Lung Slices

dc.contributor.authorKryvenko, Vitalii
dc.contributor.authorAlberro-Brage, Andrés
dc.contributor.authorFysikopoulos, Athanasios
dc.contributor.authorWessendorf, Miriam
dc.contributor.authorTello, Khodr
dc.contributor.authorMorty, Rory E.
dc.contributor.authorHerold, Susanne
dc.contributor.authorSeeger, Werner
dc.contributor.authorSamakovlis, Christos
dc.contributor.authorVadász, István
dc.date.accessioned2023-04-17T07:53:25Z
dc.date.available2023-04-17T07:53:25Z
dc.date.issued2023
dc.description.abstractA hallmark of acute respiratory distress syndrome (ARDS) is an accumulation of protein-rich alveolar edema that impairs gas exchange and leads to worse outcomes. Thus, understanding the mechanisms of alveolar albumin clearance is of high clinical relevance. Here, we investigated the mechanisms of the cellular albumin uptake in a three-dimensional culture of precision-cut lung slices (PCLS). We found that up to 60% of PCLS cells incorporated labeled albumin in a time- and concentration-dependent manner, whereas virtually no uptake of labeled dextran was observed. Of note, at a low temperature (4 °C), saturating albumin receptors with unlabeled albumin and an inhibition of clathrin-mediated endocytosis markedly decreased the endocytic uptake of the labeled protein, implicating a receptor-driven internalization process. Importantly, uptake rates of albumin were comparable in alveolar epithelial type I (ATI) and type II (ATII) cells, as assessed in PCLS from a SftpcCreERT2/+: tdTomatoflox/flox mouse strain (defined as EpCAM+CD31−CD45−tdTomatoSPC−T1α+ for ATI and EpCAM+CD31−CD45−tdTomatoSPC+T1α− for ATII cells). Once internalized, albumin was found in the early and recycling endosomes of the alveolar epithelium as well as in endothelial, mesenchymal, and hematopoietic cell populations, which might indicate transcytosis of the protein. In summary, we characterize albumin uptake in alveolar epithelial cells in the complex setting of PCLS. These findings may open new possibilities for pulmonary drug delivery that may improve the outcomes for patients with respiratory failure.
dc.description.sponsorshipDeutsche Forschungsgemeinschaft (DFG); ROR-ID:018mejw64
dc.identifier.urihttps://jlupub.ub.uni-giessen.de//handle/jlupub/16242
dc.identifier.urihttp://dx.doi.org/10.22029/jlupub-15625
dc.language.isoen
dc.rightsNamensnennung 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectprecision-cut lung slices
dc.subjectendocytosis
dc.subjectprotein transport
dc.subjectalbumin
dc.subjectalveolar epithelium
dc.subjectacute respiratory distress syndrome
dc.subject.ddcddc:610
dc.titleClathrin-Mediated Albumin Clearance in Alveolar Epithelial Cells of Murine Precision-Cut Lung Slices
dc.typearticle
local.affiliationFB 11 - Medizin
local.projectDFG/KFO309, P5; EXC 2026; Project ID: 390649896
local.source.articlenumber2644
local.source.epage15
local.source.journaltitleInternational journal of molecular sciences
local.source.spage1
local.source.urihttps://doi.org/10.3390/ijms24032644
local.source.volume24

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