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Human serum albumin-based probes for molecular targeting of macrophage scavenger receptors

Background: Inflammation and accumulation of macrophages are key features of unstable atherosclerotic plaques. The ability of macrophages to take up molecular probes can be exploited in new clinical imaging methods for the detection of unstable atherosclerotic lesions. We investigated whether modifi...

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Autores principales: Ahmed, Mona, Baumgartner, Roland, Aldi, Silvia, Dusart, Philip, Hedin, Ulf, Gustafsson, Björn, Caidahl, Kenneth
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6535103/
https://www.ncbi.nlm.nih.gov/pubmed/31190821
http://dx.doi.org/10.2147/IJN.S197990
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author Ahmed, Mona
Baumgartner, Roland
Aldi, Silvia
Dusart, Philip
Hedin, Ulf
Gustafsson, Björn
Caidahl, Kenneth
author_facet Ahmed, Mona
Baumgartner, Roland
Aldi, Silvia
Dusart, Philip
Hedin, Ulf
Gustafsson, Björn
Caidahl, Kenneth
author_sort Ahmed, Mona
collection PubMed
description Background: Inflammation and accumulation of macrophages are key features of unstable atherosclerotic plaques. The ability of macrophages to take up molecular probes can be exploited in new clinical imaging methods for the detection of unstable atherosclerotic lesions. We investigated whether modifications of human serum albumin (HSA) could be used to target macrophages efficiently in vitro. Materials and methods: Maleylated and aconitylated HSA were compared with unmodified HSA. Fluorescent or radiolabeled ((89)Zr) modified HSA was used in in vitro experiments to study cellular uptake by differentiated THP-1 cells and primary human macrophages. The time course of uptake was evaluated by flow cytometry, confocal microscopy, real-time microscopy and radioactivity measurements. The involvement of scavenger receptors (SR-A1, SR-B2, LOX-1) was assessed by knockdown experiments using RNA interference, by blocking experiments and by assays of competition by modified low-density lipoprotein. Results: Modified HSA was readily taken up by different macrophages. Uptake was mediated nonexclusively via the scavenger receptor SR-A1 (encoded by the MSR1 gene). Knockdown of CD36 and ORL1 had no influence on the uptake. Modified HSA was preferentially taken up by human macrophages compared with other vascular cell types such as endothelial cells and smooth muscle cells. Conclusions: Modified (89)Zr-labeled HSA probes were recognized by different subsets of polarized macrophages, and maleylated HSA may be a promising radiotracer for radionuclide imaging of macrophage-rich inflammatory vascular diseases.
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spelling pubmed-65351032019-06-12 Human serum albumin-based probes for molecular targeting of macrophage scavenger receptors Ahmed, Mona Baumgartner, Roland Aldi, Silvia Dusart, Philip Hedin, Ulf Gustafsson, Björn Caidahl, Kenneth Int J Nanomedicine Original Research Background: Inflammation and accumulation of macrophages are key features of unstable atherosclerotic plaques. The ability of macrophages to take up molecular probes can be exploited in new clinical imaging methods for the detection of unstable atherosclerotic lesions. We investigated whether modifications of human serum albumin (HSA) could be used to target macrophages efficiently in vitro. Materials and methods: Maleylated and aconitylated HSA were compared with unmodified HSA. Fluorescent or radiolabeled ((89)Zr) modified HSA was used in in vitro experiments to study cellular uptake by differentiated THP-1 cells and primary human macrophages. The time course of uptake was evaluated by flow cytometry, confocal microscopy, real-time microscopy and radioactivity measurements. The involvement of scavenger receptors (SR-A1, SR-B2, LOX-1) was assessed by knockdown experiments using RNA interference, by blocking experiments and by assays of competition by modified low-density lipoprotein. Results: Modified HSA was readily taken up by different macrophages. Uptake was mediated nonexclusively via the scavenger receptor SR-A1 (encoded by the MSR1 gene). Knockdown of CD36 and ORL1 had no influence on the uptake. Modified HSA was preferentially taken up by human macrophages compared with other vascular cell types such as endothelial cells and smooth muscle cells. Conclusions: Modified (89)Zr-labeled HSA probes were recognized by different subsets of polarized macrophages, and maleylated HSA may be a promising radiotracer for radionuclide imaging of macrophage-rich inflammatory vascular diseases. Dove 2019-05-21 /pmc/articles/PMC6535103/ /pubmed/31190821 http://dx.doi.org/10.2147/IJN.S197990 Text en © 2019 Ahmed et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Ahmed, Mona
Baumgartner, Roland
Aldi, Silvia
Dusart, Philip
Hedin, Ulf
Gustafsson, Björn
Caidahl, Kenneth
Human serum albumin-based probes for molecular targeting of macrophage scavenger receptors
title Human serum albumin-based probes for molecular targeting of macrophage scavenger receptors
title_full Human serum albumin-based probes for molecular targeting of macrophage scavenger receptors
title_fullStr Human serum albumin-based probes for molecular targeting of macrophage scavenger receptors
title_full_unstemmed Human serum albumin-based probes for molecular targeting of macrophage scavenger receptors
title_short Human serum albumin-based probes for molecular targeting of macrophage scavenger receptors
title_sort human serum albumin-based probes for molecular targeting of macrophage scavenger receptors
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6535103/
https://www.ncbi.nlm.nih.gov/pubmed/31190821
http://dx.doi.org/10.2147/IJN.S197990
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