Phagocytosis of Nonapoptotic Cells Dying by Caspase-Independent Mechanisms

Hirt, Ulrich; Gantner, Florian; Leist, Marcel

Phagocytosis of Nonapoptotic Cells Dying by Caspase-Independent Mechanisms

Dateien

uliphago_00.pdfGröße: 387.15 KBDownloads: 510

Datum

2000

Autor:innen

Hirt, Ulrich

Gantner, Florian

Leist, Marcel

Publikationstyp

Zeitschriftenartikel

unikn.publication.listelement.citation.prefix.version.undefined

Journal of Immunology. 2000, 164(12), pp. 6520-6529. ISSN 0022-1767. eISSN 1550-6606

Zusammenfassung

Caspase activation, exposure of phosphatidylserine (PS) on the outer surface of the plasma membrane, and rapid phagocytic removal of dying cells are key features of apoptosis. Nonapoptotic/necrotic modes of death occur independent of caspase activation, but the role of phagocytosis is largely unknown. To address this issue, we studied phagocytosis by human monocyte-derived macrophages (HMDM) and rat microglial cells. Target cells (Jurkat) were stimulated by several different methods that all caused caspase-independent death. First, we induced necrosis by combining toxins with ATP-depleting agents. Under these conditions, neither PS was exposed nor were such cells phagocytosed before their death. However, once the plasma membrane integrity was lost, the dead cells were rapidly and efficiently engulfed by HMDM. Next, we triggered Jurkat cell death with staurosporine in the presence of the pan-caspase inhibitor zVAD-fmk. Under these conditions, death occurred by delayed necrosis and without exposure of PS. Nevertheless, such lethally challenged cells were phagocytosed before the loss of membrane integrity. Finally, we triggered Ca2+ influx in Jurkat cells with an ionophore, or in neurons by glutamate receptor stimulation, respectively. In both models, PS was exposed on the cell surface. Ca2+-stressed cells were phagocytosed starting at 30 min after stimulation. Protein kinase C inhibitors prevented Ca2+-mediated PS exposure and phagocytosis. Essentially, similar phagocytosis data were obtained for all models with HMDM and microglia. We conclude that also cells dying nonapoptotically and independent of caspase activation may be recognized and removed before, or very quickly after, membrane lysis.

Fachgebiet (DDC)

570 Biowissenschaften, Biologie

Zitieren

ISO 690

HIRT, Ulrich, Florian GANTNER, Marcel LEIST, 2000. Phagocytosis of Nonapoptotic Cells Dying by Caspase-Independent Mechanisms. In: Journal of Immunology. 2000, 164(12), pp. 6520-6529. ISSN 0022-1767. eISSN 1550-6606

BibTex

@article{Hirt2000Phago-8280,
  year={2000},
  title={Phagocytosis of Nonapoptotic Cells Dying by Caspase-Independent Mechanisms},
  number={12},
  volume={164},
  issn={0022-1767},
  journal={Journal of Immunology},
  pages={6520--6529},
  author={Hirt, Ulrich and Gantner, Florian and Leist, Marcel}
}

RDF

<rdf:RDF
    xmlns:dcterms="http://purl.org/dc/terms/"
    xmlns:dc="http://purl.org/dc/elements/1.1/"
    xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#"
    xmlns:bibo="http://purl.org/ontology/bibo/"
    xmlns:dspace="http://digital-repositories.org/ontologies/dspace/0.1.0#"
    xmlns:foaf="http://xmlns.com/foaf/0.1/"
    xmlns:void="http://rdfs.org/ns/void#"
    xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > 
  <rdf:Description rdf:about="https://kops.uni-konstanz.de/server/rdf/resource/123456789/8280">
    <foaf:homepage rdf:resource="http://localhost:8080/"/>
    <dc:format>application/pdf</dc:format>
    <dc:creator>Gantner, Florian</dc:creator>
    <dc:rights>terms-of-use</dc:rights>
    <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2011-03-24T17:42:22Z</dc:date>
    <dc:contributor>Hirt, Ulrich</dc:contributor>
    <dc:creator>Hirt, Ulrich</dc:creator>
    <dc:contributor>Gantner, Florian</dc:contributor>
    <dcterms:title>Phagocytosis of Nonapoptotic Cells Dying by Caspase-Independent Mechanisms</dcterms:title>
    <dcterms:hasPart rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/8280/1/uliphago_00.pdf"/>
    <dc:creator>Leist, Marcel</dc:creator>
    <dcterms:issued>2000</dcterms:issued>
    <dcterms:abstract xml:lang="eng">Caspase activation, exposure of phosphatidylserine (PS) on the outer surface of the plasma membrane, and rapid phagocytic removal of dying cells are key features of apoptosis. Nonapoptotic/necrotic modes of death occur independent of caspase activation, but the role of phagocytosis is largely unknown. To address this issue, we studied phagocytosis by human monocyte-derived macrophages (HMDM) and rat microglial cells. Target cells (Jurkat) were stimulated by several different methods that all caused caspase-independent death. First, we induced necrosis by combining toxins with ATP-depleting agents. Under these conditions, neither PS was exposed nor were such cells phagocytosed before their death. However, once the plasma membrane integrity was lost, the dead cells were rapidly and efficiently engulfed by HMDM. Next, we triggered Jurkat cell death with staurosporine in the presence of the pan-caspase inhibitor zVAD-fmk. Under these conditions, death occurred by delayed necrosis and without exposure of PS. Nevertheless, such lethally challenged cells were phagocytosed before the loss of membrane integrity. Finally, we triggered Ca2+ influx in Jurkat cells with an ionophore, or in neurons by glutamate receptor stimulation, respectively. In both models, PS was exposed on the cell surface. Ca2+-stressed cells were phagocytosed starting at 30 min after stimulation. Protein kinase C inhibitors prevented Ca2+-mediated PS exposure and phagocytosis. Essentially, similar phagocytosis data were obtained for all models with HMDM and microglia. We conclude that also cells dying nonapoptotically and independent of caspase activation may be recognized and removed before, or very quickly after, membrane lysis.</dcterms:abstract>
    <bibo:uri rdf:resource="http://kops.uni-konstanz.de/handle/123456789/8280"/>
    <dcterms:rights rdf:resource="https://rightsstatements.org/page/InC/1.0/"/>
    <dc:language>eng</dc:language>
    <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/>
    <dspace:hasBitstream rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/8280/1/uliphago_00.pdf"/>
    <dcterms:bibliographicCitation>First publ. in: Journal of Immunology ; 164 (2000), 12. - pp. 6520-6529</dcterms:bibliographicCitation>
    <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/>
    <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2011-03-24T17:42:22Z</dcterms:available>
    <dc:contributor>Leist, Marcel</dc:contributor>
    <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/>
  </rdf:Description>
</rdf:RDF>

Universitätsbibliographie

Nein