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Inhibition of “self” engulfment through deactivation of myosin-II at the phagocytic synapse between human cells
Phagocytosis of foreign cells or particles by macrophages is a rapid process that is inefficient when faced with “self” cells that display CD47—although signaling mechanisms in self-recognition have remained largely unknown. With human macrophages, we show the phagocytic synapse at cell contacts inv...
Autores principales: | , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2008
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2265407/ https://www.ncbi.nlm.nih.gov/pubmed/18332220 http://dx.doi.org/10.1083/jcb.200708043 |
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author | Tsai, Richard K. Discher, Dennis E. |
author_facet | Tsai, Richard K. Discher, Dennis E. |
author_sort | Tsai, Richard K. |
collection | PubMed |
description | Phagocytosis of foreign cells or particles by macrophages is a rapid process that is inefficient when faced with “self” cells that display CD47—although signaling mechanisms in self-recognition have remained largely unknown. With human macrophages, we show the phagocytic synapse at cell contacts involves a basal level of actin-driven phagocytosis that, in the absence of species-specific CD47 signaling, is made more efficient by phospho-activated myosin. We use “foreign” sheep red blood cells (RBCs) together with CD47-blocked, antibody-opsonized human RBCs in order to visualize synaptic accumulation of phosphotyrosine, paxillin, F-actin, and the major motor isoform, nonmuscle myosin-IIA. When CD47 is functional, the macrophage counter-receptor and phosphatase-activator SIRPα localizes to the synapse, suppressing accumulation of phosphotyrosine and myosin without affecting F-actin. On both RBCs and microbeads, human CD47 potently inhibits phagocytosis as does direct inhibition of myosin. CD47–SIRPα interaction initiates a dephosphorylation cascade directed in part at phosphotyrosine in myosin. A point mutation turns off this motor's contribution to phagocytosis, suggesting that self-recognition inhibits contractile engulfment. |
format | Text |
id | pubmed-2265407 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-22654072008-09-10 Inhibition of “self” engulfment through deactivation of myosin-II at the phagocytic synapse between human cells Tsai, Richard K. Discher, Dennis E. J Cell Biol Research Articles Phagocytosis of foreign cells or particles by macrophages is a rapid process that is inefficient when faced with “self” cells that display CD47—although signaling mechanisms in self-recognition have remained largely unknown. With human macrophages, we show the phagocytic synapse at cell contacts involves a basal level of actin-driven phagocytosis that, in the absence of species-specific CD47 signaling, is made more efficient by phospho-activated myosin. We use “foreign” sheep red blood cells (RBCs) together with CD47-blocked, antibody-opsonized human RBCs in order to visualize synaptic accumulation of phosphotyrosine, paxillin, F-actin, and the major motor isoform, nonmuscle myosin-IIA. When CD47 is functional, the macrophage counter-receptor and phosphatase-activator SIRPα localizes to the synapse, suppressing accumulation of phosphotyrosine and myosin without affecting F-actin. On both RBCs and microbeads, human CD47 potently inhibits phagocytosis as does direct inhibition of myosin. CD47–SIRPα interaction initiates a dephosphorylation cascade directed in part at phosphotyrosine in myosin. A point mutation turns off this motor's contribution to phagocytosis, suggesting that self-recognition inhibits contractile engulfment. The Rockefeller University Press 2008-03-10 /pmc/articles/PMC2265407/ /pubmed/18332220 http://dx.doi.org/10.1083/jcb.200708043 Text en Copyright © 2008, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Research Articles Tsai, Richard K. Discher, Dennis E. Inhibition of “self” engulfment through deactivation of myosin-II at the phagocytic synapse between human cells |
title | Inhibition of “self” engulfment through deactivation of myosin-II at the phagocytic synapse between human cells |
title_full | Inhibition of “self” engulfment through deactivation of myosin-II at the phagocytic synapse between human cells |
title_fullStr | Inhibition of “self” engulfment through deactivation of myosin-II at the phagocytic synapse between human cells |
title_full_unstemmed | Inhibition of “self” engulfment through deactivation of myosin-II at the phagocytic synapse between human cells |
title_short | Inhibition of “self” engulfment through deactivation of myosin-II at the phagocytic synapse between human cells |
title_sort | inhibition of “self” engulfment through deactivation of myosin-ii at the phagocytic synapse between human cells |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2265407/ https://www.ncbi.nlm.nih.gov/pubmed/18332220 http://dx.doi.org/10.1083/jcb.200708043 |
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