Cargando…

Polyethylene glycol 20 kDa-induced vacuolation does not impair phagocytic function of human monocyte-derived macrophages

Conjugation to polyethylene glycol (PEG) is commonly used to enhance drug delivery and efficacy by extending the half-life of the drug molecule. This has important implications for reducing treatment burden in diseases that require chronic prophylaxis, such as hemophilia. Clearance of PEG molecules...

Descripción completa

Detalles Bibliográficos
Autores principales: Schoenbrunn, Anne, Juelke, Kerstin, Reipert, Birgit M., Horling, Frank, Turecek, Peter L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9366735/
https://www.ncbi.nlm.nih.gov/pubmed/35967311
http://dx.doi.org/10.3389/fimmu.2022.894411
_version_ 1784765632449871872
author Schoenbrunn, Anne
Juelke, Kerstin
Reipert, Birgit M.
Horling, Frank
Turecek, Peter L.
author_facet Schoenbrunn, Anne
Juelke, Kerstin
Reipert, Birgit M.
Horling, Frank
Turecek, Peter L.
author_sort Schoenbrunn, Anne
collection PubMed
description Conjugation to polyethylene glycol (PEG) is commonly used to enhance drug delivery and efficacy by extending the half-life of the drug molecule. This has important implications for reducing treatment burden in diseases that require chronic prophylaxis, such as hemophilia. Clearance of PEG molecules with high molecular weights (≥ 40 kDa) has been reported to cause cellular vacuolation in mammals. Rurioctocog alfa pegol (PEGylated recombinant coagulation factor VIII) contains a 20-kDa PEG. This study investigated the effects of exposure to 20-kDa PEG (10 μg/ml to 10 mg/ml) on the morphology and function of human monocyte-derived macrophages (MDMs) in vitro. Exposure to PEG for 24 hours was associated with significant vacuolation only at concentrations of 1 mg/ml or more, which far exceed the levels associated with clinically relevant doses of rurioctocog alfa pegol. Immunofluorescence staining of PEG was detected in the cytoplasm of MDMs, indicating uptake into the cells. No impairment of MDM phagocytic activity (ability to ingest fluorescently labeled Escherichia coli) was observed with 24-hour exposure to PEG, even at concentrations associated with significant vacuolation. Furthermore, PEG exposure did not have significant effects on cytokine secretion in resting or lipopolysaccharide-stimulated MDMs, or on the expression of cell surface markers in stimulated MDMs. Cell viability was not affected by 24-hour exposure to PEG. In conclusion, vacuolation of human MDMs after exposure to 20-kDa PEG only occurred with PEG concentrations far in excess of those equivalent to clinically relevant doses of rurioctocog alfa pegol and did not affect MDM viability or functionality. Together, these results support the concept that PEG-mediated vacuolation is an adaptive cellular response rather than a toxic effect.
format Online
Article
Text
id pubmed-9366735
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-93667352022-08-12 Polyethylene glycol 20 kDa-induced vacuolation does not impair phagocytic function of human monocyte-derived macrophages Schoenbrunn, Anne Juelke, Kerstin Reipert, Birgit M. Horling, Frank Turecek, Peter L. Front Immunol Immunology Conjugation to polyethylene glycol (PEG) is commonly used to enhance drug delivery and efficacy by extending the half-life of the drug molecule. This has important implications for reducing treatment burden in diseases that require chronic prophylaxis, such as hemophilia. Clearance of PEG molecules with high molecular weights (≥ 40 kDa) has been reported to cause cellular vacuolation in mammals. Rurioctocog alfa pegol (PEGylated recombinant coagulation factor VIII) contains a 20-kDa PEG. This study investigated the effects of exposure to 20-kDa PEG (10 μg/ml to 10 mg/ml) on the morphology and function of human monocyte-derived macrophages (MDMs) in vitro. Exposure to PEG for 24 hours was associated with significant vacuolation only at concentrations of 1 mg/ml or more, which far exceed the levels associated with clinically relevant doses of rurioctocog alfa pegol. Immunofluorescence staining of PEG was detected in the cytoplasm of MDMs, indicating uptake into the cells. No impairment of MDM phagocytic activity (ability to ingest fluorescently labeled Escherichia coli) was observed with 24-hour exposure to PEG, even at concentrations associated with significant vacuolation. Furthermore, PEG exposure did not have significant effects on cytokine secretion in resting or lipopolysaccharide-stimulated MDMs, or on the expression of cell surface markers in stimulated MDMs. Cell viability was not affected by 24-hour exposure to PEG. In conclusion, vacuolation of human MDMs after exposure to 20-kDa PEG only occurred with PEG concentrations far in excess of those equivalent to clinically relevant doses of rurioctocog alfa pegol and did not affect MDM viability or functionality. Together, these results support the concept that PEG-mediated vacuolation is an adaptive cellular response rather than a toxic effect. Frontiers Media S.A. 2022-07-28 /pmc/articles/PMC9366735/ /pubmed/35967311 http://dx.doi.org/10.3389/fimmu.2022.894411 Text en Copyright © 2022 Schoenbrunn, Juelke, Reipert, Horling and Turecek https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Schoenbrunn, Anne
Juelke, Kerstin
Reipert, Birgit M.
Horling, Frank
Turecek, Peter L.
Polyethylene glycol 20 kDa-induced vacuolation does not impair phagocytic function of human monocyte-derived macrophages
title Polyethylene glycol 20 kDa-induced vacuolation does not impair phagocytic function of human monocyte-derived macrophages
title_full Polyethylene glycol 20 kDa-induced vacuolation does not impair phagocytic function of human monocyte-derived macrophages
title_fullStr Polyethylene glycol 20 kDa-induced vacuolation does not impair phagocytic function of human monocyte-derived macrophages
title_full_unstemmed Polyethylene glycol 20 kDa-induced vacuolation does not impair phagocytic function of human monocyte-derived macrophages
title_short Polyethylene glycol 20 kDa-induced vacuolation does not impair phagocytic function of human monocyte-derived macrophages
title_sort polyethylene glycol 20 kda-induced vacuolation does not impair phagocytic function of human monocyte-derived macrophages
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9366735/
https://www.ncbi.nlm.nih.gov/pubmed/35967311
http://dx.doi.org/10.3389/fimmu.2022.894411
work_keys_str_mv AT schoenbrunnanne polyethyleneglycol20kdainducedvacuolationdoesnotimpairphagocyticfunctionofhumanmonocytederivedmacrophages
AT juelkekerstin polyethyleneglycol20kdainducedvacuolationdoesnotimpairphagocyticfunctionofhumanmonocytederivedmacrophages
AT reipertbirgitm polyethyleneglycol20kdainducedvacuolationdoesnotimpairphagocyticfunctionofhumanmonocytederivedmacrophages
AT horlingfrank polyethyleneglycol20kdainducedvacuolationdoesnotimpairphagocyticfunctionofhumanmonocytederivedmacrophages
AT turecekpeterl polyethyleneglycol20kdainducedvacuolationdoesnotimpairphagocyticfunctionofhumanmonocytederivedmacrophages