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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...

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Autores principales: Tsai, Richard K., Discher, Dennis E.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2008
Materias:
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.
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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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