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Immunoglobulin-mediated phagocytosis by human monocytes requires protein kinase C activation. Evidence for protein kinase C translocation to phagosomes
Open accessAbstract
This study has investigated the role of protein kinase C (PKC) activation in IgG-mediated phagocytosis by human monocytes. Incubation of monocytes with IgG-opsonized targets increased membrane-associated PKC approximately 2-fold. Kinetic studies showed that the translocation of PKC to membrane occurred before significant ingestion took place. The pharmacologic PKC inhibitor H7 inhibited IgG-dependent ingestion with ID50 of 20 microM, while the structurally related isoquinoline sulfonamide HA1004 had no effect at this concentration. Staurosporine and calphostin C, PKC inhibitors which have different mechanisms of actions than H7, also inhibited ingestion. Depletion of PKC by prolonged incubation with phorbol esters also inhibited phagocytosis, and dose-response curves showed a strong correlation between the extent of PKC depletion and the extent of inhibition of ingestion. Finally, phagosomes were isolated by sucrose density centrifugation of cells disrupted 5 min after the initiation of phagocytosis. Measurement of PKC activity and immunoreactivity in the phagosomes showed that PKC was concentrated in the phagosome membrane approximately 5-fold compared to the uninvolved plasma membrane. Together, these data suggest that PKC activation is an early, essential step in the efficient ingestion of IgG-opsonized targets by monocytes.
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“both PKCα and PKCδ copurify with isolated phagosomal membranes (Allen and Aderem 1995; Brumell et al. 1999) and some inhibitors of PKC activity have been reported to interfere with phagocytosis (Zheleznyak and Brown 1992; Karimi et al. 1999).”
From Localized Biphasic Changes in Phosphatidylinositol-4,5-Bisphosphate at Sites of Phagocytosis (2000) · cites this paper as Zheleznyak and Brown 1992
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Metadata
- Authors
- Zheleznyak, A., & Brown, E. J.
- Affiliations
- Washington University in St. Louis (US)
- ORCID
- Brown, E.J.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1992-06
- Volume
- 267
- Issue
- 17
- Pages
- 12042-12048
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1567522204
- Cited by
- 118
- References
- 27
- Citations by year
- 2024: 4 · 2022: 1 · 2021: 3 · 2017: 1 · 2016: 1 · 2015: 1 · 2014: 3 · 2013: 3 · 2012: 1
- FWCI
- 2.09
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (GM38330, R01GM038330)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- protein kinase C, phagocytosis, monocytes, IgG opsonization, phagosome, PKC translocation, PKC inhibitors, H7, staurosporine, calphostin C, phorbol ester
- MeSH terms
- Alkaline Phosphatase, Alkaloids, Amino Acid Sequence, Biological Transport, Electrophoresis, Polyacrylamide Gel, Enzyme Activation, Eye Proteins, Humans, Immunoglobulin G, Isoquinolines, Kinetics, Molecular Sequence Data, Monocytes, Naphthalenes, Phagocytosis, Phagosomes, Piperazines, Polycyclic Compounds, Protein Kinase C, Sulfonamides, Blotting, Western, Signal Transduction, Rod Opsins, 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine, Staurosporine
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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