PMID- 36768968
OWN - NLM
STAT- MEDLINE
DCOM- 20230214
LR  - 20230214
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 24
IP  - 3
DP  - 2023 Jan 31
TI  - Clathrin-Mediated Albumin Clearance in Alveolar Epithelial Cells of Murine 
      Precision-Cut Lung Slices.
LID - 10.3390/ijms24032644 [doi]
LID - 2644
AB  - A 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  degrees 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 SftpcCre(ERT2/+): tdTomato(flox/flox) mouse 
      strain (defined as EpCAM(+)CD31(-)CD45(-)tdTomatoSPC(-)T1alpha(+) for ATI and 
      EpCAM(+)CD31(-)CD45(-)tdTomatoSPC(+)T1alpha(-) 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.
FAU - Kryvenko, Vitalii
AU  - Kryvenko V
AUID- ORCID: 0000-0002-5683-4990
AD  - Department of Internal Medicine, Justus Liebig University, Universities of 
      Giessen and Marburg Lung Center (UGMLC), 35392 Giessen, Germany.
AD  - German Center for Lung Research (DZL), 35392 Giessen, Germany.
AD  - The Cardio-Pulmonary Institute (CPI), 35392 Giessen, Germany.
AD  - Institute for Lung Health (ILH), 35392 Giessen, Germany.
FAU - Alberro-Brage, Andres
AU  - Alberro-Brage A
AUID- ORCID: 0000-0001-8158-544X
AD  - Department of Internal Medicine, Justus Liebig University, Universities of 
      Giessen and Marburg Lung Center (UGMLC), 35392 Giessen, Germany.
AD  - German Center for Lung Research (DZL), 35392 Giessen, Germany.
AD  - The Cardio-Pulmonary Institute (CPI), 35392 Giessen, Germany.
FAU - Fysikopoulos, Athanasios
AU  - Fysikopoulos A
AUID- ORCID: 0000-0002-8081-0198
AD  - Department of Internal Medicine, Justus Liebig University, Universities of 
      Giessen and Marburg Lung Center (UGMLC), 35392 Giessen, Germany.
FAU - Wessendorf, Miriam
AU  - Wessendorf M
AD  - Department of Internal Medicine, Justus Liebig University, Universities of 
      Giessen and Marburg Lung Center (UGMLC), 35392 Giessen, Germany.
AD  - Institute for Lung Health (ILH), 35392 Giessen, Germany.
FAU - Tello, Khodr
AU  - Tello K
AD  - Department of Internal Medicine, Justus Liebig University, Universities of 
      Giessen and Marburg Lung Center (UGMLC), 35392 Giessen, Germany.
AD  - German Center for Lung Research (DZL), 35392 Giessen, Germany.
AD  - The Cardio-Pulmonary Institute (CPI), 35392 Giessen, Germany.
AD  - Institute for Lung Health (ILH), 35392 Giessen, Germany.
FAU - Morty, Rory E
AU  - Morty RE
AD  - German Center for Lung Research (DZL), 35392 Giessen, Germany.
AD  - Department of Lung Development and Remodeling, Max Planck Institute for Heart and 
      Lung Research, 61231 Bad Nauheim, Germany.
AD  - Department of Translational Pulmonology, and Translational Lung Research Center 
      (TLRC), 69120 Heidelberg, Germany.
FAU - Herold, Susanne
AU  - Herold S
AD  - Department of Internal Medicine, Justus Liebig University, Universities of 
      Giessen and Marburg Lung Center (UGMLC), 35392 Giessen, Germany.
AD  - German Center for Lung Research (DZL), 35392 Giessen, Germany.
AD  - The Cardio-Pulmonary Institute (CPI), 35392 Giessen, Germany.
AD  - Institute for Lung Health (ILH), 35392 Giessen, Germany.
FAU - Seeger, Werner
AU  - Seeger W
AD  - Department of Internal Medicine, Justus Liebig University, Universities of 
      Giessen and Marburg Lung Center (UGMLC), 35392 Giessen, Germany.
AD  - German Center for Lung Research (DZL), 35392 Giessen, Germany.
AD  - The Cardio-Pulmonary Institute (CPI), 35392 Giessen, Germany.
AD  - Institute for Lung Health (ILH), 35392 Giessen, Germany.
AD  - Department of Lung Development and Remodeling, Max Planck Institute for Heart and 
      Lung Research, 61231 Bad Nauheim, Germany.
FAU - Samakovlis, Christos
AU  - Samakovlis C
AD  - Department of Internal Medicine, Justus Liebig University, Universities of 
      Giessen and Marburg Lung Center (UGMLC), 35392 Giessen, Germany.
AD  - German Center for Lung Research (DZL), 35392 Giessen, Germany.
AD  - The Cardio-Pulmonary Institute (CPI), 35392 Giessen, Germany.
AD  - Institute for Lung Health (ILH), 35392 Giessen, Germany.
AD  - Science for Life Laboratory, Department of Molecular Biosciences, The Wenner-Gren 
      Institute, Stockholm University, SE-10691 Stockholm, Sweden.
FAU - Vadasz, Istvan
AU  - Vadasz I
AD  - Department of Internal Medicine, Justus Liebig University, Universities of 
      Giessen and Marburg Lung Center (UGMLC), 35392 Giessen, Germany.
AD  - German Center for Lung Research (DZL), 35392 Giessen, Germany.
AD  - The Cardio-Pulmonary Institute (CPI), 35392 Giessen, Germany.
AD  - Institute for Lung Health (ILH), 35392 Giessen, Germany.
LA  - eng
GR  - DFG/KFO309, P5/Deutsche Forschungsgemeinschaft/
GR  - EXC 2026; Project ID: 390649896/Deutsche Forschungsgemeinschaft/
GR  - DZL/ALI 1.5 and 3.4/Federal Ministry of Education and Research/
GR  - Project 66-LV07/Von Behring-Rontgen-Stiftung/
PT  - Journal Article
DEP - 20230131
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Epithelial Cell Adhesion Molecule)
RN  - 0 (Clathrin)
RN  - 0 (Serum Albumin)
SB  - IM
MH  - Mice
MH  - Animals
MH  - *Alveolar Epithelial Cells/metabolism
MH  - Epithelial Cell Adhesion Molecule/metabolism
MH  - *Clathrin/metabolism
MH  - Lung/metabolism
MH  - Epithelial Cells/metabolism
MH  - Serum Albumin/metabolism
MH  - Pulmonary Alveoli/metabolism
PMC - PMC9916738
OTO - NOTNLM
OT  - acute respiratory distress syndrome
OT  - albumin
OT  - alveolar epithelium
OT  - endocytosis
OT  - precision-cut lung slices
OT  - protein transport
COIS- The authors declare no conflict of interest.
EDAT- 2023/02/12 06:00
MHDA- 2023/02/15 06:00
PMCR- 2023/01/31
CRDT- 2023/02/11 01:23
PHST- 2022/12/26 00:00 [received]
PHST- 2023/01/19 00:00 [revised]
PHST- 2023/01/23 00:00 [accepted]
PHST- 2023/02/11 01:23 [entrez]
PHST- 2023/02/12 06:00 [pubmed]
PHST- 2023/02/15 06:00 [medline]
PHST- 2023/01/31 00:00 [pmc-release]
AID - ijms24032644 [pii]
AID - ijms-24-02644 [pii]
AID - 10.3390/ijms24032644 [doi]
PST - epublish
SO  - Int J Mol Sci. 2023 Jan 31;24(3):2644. doi: 10.3390/ijms24032644.