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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...

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Detalles Bibliográficos
Autores principales: Pontejo, Sergio M., Murphy, Philip M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
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.
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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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