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Chemokines act as phosphatidylserine-bound “find-me” signals in apoptotic cell clearance
Removal of apoptotic cells is essential for maintenance of tissue homeostasis. Chemotactic cues termed “find-me” signals attract phagocytes toward apoptotic cells, which selectively expose the anionic phospholipid phosphatidylserine (PS) and other “eat-me” signals to distinguish healthy from apoptot...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213124/ https://www.ncbi.nlm.nih.gov/pubmed/34038417 http://dx.doi.org/10.1371/journal.pbio.3001259 |
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author | Pontejo, Sergio M. Murphy, Philip M. |
author_facet | Pontejo, Sergio M. Murphy, Philip M. |
author_sort | Pontejo, Sergio M. |
collection | PubMed |
description | Removal of apoptotic cells is essential for maintenance of tissue homeostasis. Chemotactic cues termed “find-me” signals attract phagocytes toward apoptotic cells, which selectively expose the anionic phospholipid phosphatidylserine (PS) and other “eat-me” signals to distinguish healthy from apoptotic cells for phagocytosis. Blebs released by apoptotic cells can deliver find-me signals; however, the mechanism is poorly understood. Here, we demonstrate that apoptotic blebs generated in vivo from mouse thymus attract phagocytes using endogenous chemokines bound to the bleb surface. We show that chemokine binding to apoptotic cells is mediated by PS and that high affinity binding of PS and other anionic phospholipids is a general property of many but not all chemokines. Chemokines are positively charged proteins that also bind to anionic glycosaminoglycans (GAGs) on cell surfaces for presentation to leukocyte G protein–coupled receptors (GPCRs). We found that apoptotic cells down-regulate GAGs as they up-regulate PS on the cell surface and that PS-bound chemokines, unlike GAG-bound chemokines, are able to directly activate chemokine receptors. Thus, we conclude that PS-bound chemokines may serve as find-me signals on apoptotic vesicles acting at cognate chemokine receptors on leukocytes. |
format | Online Article Text |
id | pubmed-8213124 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-82131242021-06-29 Chemokines act as phosphatidylserine-bound “find-me” signals in apoptotic cell clearance Pontejo, Sergio M. Murphy, Philip M. PLoS Biol Research Article Removal of apoptotic cells is essential for maintenance of tissue homeostasis. Chemotactic cues termed “find-me” signals attract phagocytes toward apoptotic cells, which selectively expose the anionic phospholipid phosphatidylserine (PS) and other “eat-me” signals to distinguish healthy from apoptotic cells for phagocytosis. Blebs released by apoptotic cells can deliver find-me signals; however, the mechanism is poorly understood. Here, we demonstrate that apoptotic blebs generated in vivo from mouse thymus attract phagocytes using endogenous chemokines bound to the bleb surface. We show that chemokine binding to apoptotic cells is mediated by PS and that high affinity binding of PS and other anionic phospholipids is a general property of many but not all chemokines. Chemokines are positively charged proteins that also bind to anionic glycosaminoglycans (GAGs) on cell surfaces for presentation to leukocyte G protein–coupled receptors (GPCRs). We found that apoptotic cells down-regulate GAGs as they up-regulate PS on the cell surface and that PS-bound chemokines, unlike GAG-bound chemokines, are able to directly activate chemokine receptors. Thus, we conclude that PS-bound chemokines may serve as find-me signals on apoptotic vesicles acting at cognate chemokine receptors on leukocytes. Public Library of Science 2021-05-26 /pmc/articles/PMC8213124/ /pubmed/34038417 http://dx.doi.org/10.1371/journal.pbio.3001259 Text en https://creativecommons.org/publicdomain/zero/1.0/This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 (https://creativecommons.org/publicdomain/zero/1.0/) public domain dedication. |
spellingShingle | Research Article Pontejo, Sergio M. Murphy, Philip M. Chemokines act as phosphatidylserine-bound “find-me” signals in apoptotic cell clearance |
title | Chemokines act as phosphatidylserine-bound “find-me” signals in apoptotic cell clearance |
title_full | Chemokines act as phosphatidylserine-bound “find-me” signals in apoptotic cell clearance |
title_fullStr | Chemokines act as phosphatidylserine-bound “find-me” signals in apoptotic cell clearance |
title_full_unstemmed | Chemokines act as phosphatidylserine-bound “find-me” signals in apoptotic cell clearance |
title_short | Chemokines act as phosphatidylserine-bound “find-me” signals in apoptotic cell clearance |
title_sort | chemokines act as phosphatidylserine-bound “find-me” signals in apoptotic cell clearance |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213124/ https://www.ncbi.nlm.nih.gov/pubmed/34038417 http://dx.doi.org/10.1371/journal.pbio.3001259 |
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