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...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2021-05-01
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| Series: | PLoS Biology |
| Online Access: | https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3001259&type=printable |
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| author | Sergio M Pontejo Philip M Murphy |
| author_facet | Sergio M Pontejo Philip M Murphy |
| author_sort | Sergio M Pontejo |
| collection | DOAJ |
| 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 | Article |
| id | doaj-art-cd4dc29d75134887b2129637de3f932f |
| institution | DOAJ |
| issn | 1544-9173 1545-7885 |
| language | English |
| publishDate | 2021-05-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Biology |
| spelling | doaj-art-cd4dc29d75134887b2129637de3f932f2025-08-20T02:55:20ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852021-05-01195e300125910.1371/journal.pbio.3001259Chemokines act as phosphatidylserine-bound "find-me" signals in apoptotic cell clearance.Sergio M PontejoPhilip M MurphyRemoval 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.https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3001259&type=printable |
| spellingShingle | Sergio M Pontejo Philip M Murphy Chemokines act as phosphatidylserine-bound "find-me" signals in apoptotic cell clearance. PLoS Biology |
| 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 |
| url | https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3001259&type=printable |
| work_keys_str_mv | AT sergiompontejo chemokinesactasphosphatidylserineboundfindmesignalsinapoptoticcellclearance AT philipmmurphy chemokinesactasphosphatidylserineboundfindmesignalsinapoptoticcellclearance |