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Serum-dependent processing of late apoptotic cells for enhanced efferocytosis

Binding of the serum protein complement component C1q to the surface of dying cells facilitates their clearance by phagocytes in a process termed efferocytosis. Here, we investigate during which phase of apoptotic cell death progression C1q binding takes place. Purified C1q was found to bind to all...

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Autores principales: Liang, Y Y, Arnold, T, Michlmayr, A, Rainprecht, D, Perticevic, B, Spittler, A, Oehler, R
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4047901/
https://www.ncbi.nlm.nih.gov/pubmed/24874736
http://dx.doi.org/10.1038/cddis.2014.210
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author Liang, Y Y
Arnold, T
Michlmayr, A
Rainprecht, D
Perticevic, B
Spittler, A
Oehler, R
author_facet Liang, Y Y
Arnold, T
Michlmayr, A
Rainprecht, D
Perticevic, B
Spittler, A
Oehler, R
author_sort Liang, Y Y
collection PubMed
description Binding of the serum protein complement component C1q to the surface of dying cells facilitates their clearance by phagocytes in a process termed efferocytosis. Here, we investigate during which phase of apoptotic cell death progression C1q binding takes place. Purified C1q was found to bind to all dying cells and, albeit weaker, also to viable cells. The presence of serum abrogated completely the binding to viable cells. In addition, C1q binding to dying cells was limited to a specific subpopulation of late apoptotic/secondary necrotic cells. Co-culturing serum-treated apoptotic cells with human monocytes revealed a much higher phagocytosis of C1q-positive than of C1q-negative late apoptotic/secondary necrotic cells. But this phagocytosis-promoting activity could not be observed with purified C1q. Serum-treated C1q-positive late apoptotic/secondary necrotic cells exhibited a similar volume, a similar degraded protein composition, but a much lower DNA content in comparison with the remaining late apoptotic/secondary necrotic cells. This was mediated by a serum-bound nuclease activity that could be abrogated by G-actin, which is a specific inhibitor of serum DNase I. These results show that serum factors are involved in the prevention of C1q binding to viable cells and in the processing of late apoptotic/secondary necrotic cells promoting cell death progression toward apoptotic bodies. This process leads to the exposure of C1q-binding structures and facilitates efferocytosis.
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spelling pubmed-40479012014-06-12 Serum-dependent processing of late apoptotic cells for enhanced efferocytosis Liang, Y Y Arnold, T Michlmayr, A Rainprecht, D Perticevic, B Spittler, A Oehler, R Cell Death Dis Original Article Binding of the serum protein complement component C1q to the surface of dying cells facilitates their clearance by phagocytes in a process termed efferocytosis. Here, we investigate during which phase of apoptotic cell death progression C1q binding takes place. Purified C1q was found to bind to all dying cells and, albeit weaker, also to viable cells. The presence of serum abrogated completely the binding to viable cells. In addition, C1q binding to dying cells was limited to a specific subpopulation of late apoptotic/secondary necrotic cells. Co-culturing serum-treated apoptotic cells with human monocytes revealed a much higher phagocytosis of C1q-positive than of C1q-negative late apoptotic/secondary necrotic cells. But this phagocytosis-promoting activity could not be observed with purified C1q. Serum-treated C1q-positive late apoptotic/secondary necrotic cells exhibited a similar volume, a similar degraded protein composition, but a much lower DNA content in comparison with the remaining late apoptotic/secondary necrotic cells. This was mediated by a serum-bound nuclease activity that could be abrogated by G-actin, which is a specific inhibitor of serum DNase I. These results show that serum factors are involved in the prevention of C1q binding to viable cells and in the processing of late apoptotic/secondary necrotic cells promoting cell death progression toward apoptotic bodies. This process leads to the exposure of C1q-binding structures and facilitates efferocytosis. Nature Publishing Group 2014-05 2014-05-29 /pmc/articles/PMC4047901/ /pubmed/24874736 http://dx.doi.org/10.1038/cddis.2014.210 Text en Copyright © 2014 Macmillan Publishers Limited http://creativecommons.org/licenses/by/3.0/ Cell Death and Disease is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution 3.0 Unported License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/3.0/
spellingShingle Original Article
Liang, Y Y
Arnold, T
Michlmayr, A
Rainprecht, D
Perticevic, B
Spittler, A
Oehler, R
Serum-dependent processing of late apoptotic cells for enhanced efferocytosis
title Serum-dependent processing of late apoptotic cells for enhanced efferocytosis
title_full Serum-dependent processing of late apoptotic cells for enhanced efferocytosis
title_fullStr Serum-dependent processing of late apoptotic cells for enhanced efferocytosis
title_full_unstemmed Serum-dependent processing of late apoptotic cells for enhanced efferocytosis
title_short Serum-dependent processing of late apoptotic cells for enhanced efferocytosis
title_sort serum-dependent processing of late apoptotic cells for enhanced efferocytosis
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4047901/
https://www.ncbi.nlm.nih.gov/pubmed/24874736
http://dx.doi.org/10.1038/cddis.2014.210
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